Heterogeneous Nuclear Ribonucleoproteins: Implications in Neurological Diseases.
ALS
Alzheimer’s disease
FTD
Multiple sclerosis
hnRNPs
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
29
06
2020
accepted:
17
09
2020
pubmed:
2
10
2020
medline:
2
9
2021
entrez:
1
10
2020
Statut:
ppublish
Résumé
Heterogenous nuclear ribonucleoproteins (hnRNPs) are a complex and functionally diverse family of RNA binding proteins with multifarious roles. They are involved, directly or indirectly, in alternative splicing, transcriptional and translational regulation, stress granule formation, cell cycle regulation, and axonal transport. It is unsurprising, given their heavy involvement in maintaining functional integrity of the cell, that their dysfunction has neurological implications. However, compared to their more established roles in cancer, the evidence of hnRNP implication in neurological diseases is still in its infancy. This review aims to consolidate the evidences for hnRNP involvement in neurological diseases, with a focus on spinal muscular atrophy (SMA), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), multiple sclerosis (MS), congenital myasthenic syndrome (CMS), and fragile X-associated tremor/ataxia syndrome (FXTAS). Understanding more about hnRNP involvement in neurological diseases can further elucidate the pathomechanisms involved in these diseases and perhaps guide future therapeutic advances.
Identifiants
pubmed: 33000450
doi: 10.1007/s12035-020-02137-4
pii: 10.1007/s12035-020-02137-4
pmc: PMC7843550
doi:
Substances chimiques
Heterogeneous-Nuclear Ribonucleoproteins
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
631-646Commentaires et corrections
Type : CommentIn
Références
Dreyfuss G, Matunis MJ, Pinol-Roma S, Burd CG (1993) hnRNP proteins and the biogenesis of mRNA. Anna Rev Biochem 62:289–321
doi: 10.1146/annurev.bi.62.070193.001445
Piñol-Roma S, Choi YD, Matunis MJ, Dreyfuss G (1988) Immunopurification of heterogeneous nuclear ribonucleoprotein particles reveals an assortment of RNA-binding proteins. Genes Dev 2:215–227. https://doi.org/10.1101/gad.2.2.215
doi: 10.1101/gad.2.2.215
pubmed: 3129338
Piñol-Roma S, Dreyfuss G (1992) Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. Nature. 355:730–732. https://doi.org/10.1038/355730a0
doi: 10.1038/355730a0
pubmed: 1371331
Maris C, Dominguez C, Allain FHT (2005) The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression. FEBS J 272:2118–2131. https://doi.org/10.1111/j.1742-4658.2005.04653.x
doi: 10.1111/j.1742-4658.2005.04653.x
pubmed: 15853797
Nagai K, Oubridge C, Jessen TH, Li J, Evans PR (1990) Crystal structure of the RNA-binding domain of the U1 small nuclear ribonucleoprotein a. Nature. 348:515–520. https://doi.org/10.1038/348515a0
doi: 10.1038/348515a0
pubmed: 2147232
Avis JM, Allain FHT, Howe PWA, Varani G, Nagai K, Neuhaus D (1996) Solution structure of the N-terminal RNP domain of U1A protein: The role of C-terminal residues in structure stability and RNA binding. J Mol Biol 257:398–411. https://doi.org/10.1006/jmbi.1996.0171
doi: 10.1006/jmbi.1996.0171
pubmed: 8609632
Xu RM, Jokhan L, Cheng X, Mayeda A, Krainer AR (1997) Crystal structure of human UP1, the domain of hnRNP A1 that contains two RNA-recognition motifs, structure. https://doi.org/10.1016/S0969-2126(97)00211-6 .
Shamoo Y, Krueger U, Rice LM, Williams KR, Steitz TA (1997) Crystal structure of the two RNA binding domains of human hnRNP A1 at 1.75 A resolution. Nat Struct Biol. https://doi.org/10.1038/nsb0397-215 .
Baber JL, Libutti D, Levens D, Tjandra N (1999) High precision solution structure of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K, a c-myc transcription factor. J Mol Biol. https://doi.org/10.1006/jmbi.1999.2818 .
Masuzawa T, Oyoshi T, Roles of the RGG domain and RNA recognition motif of nucleolin in G-quadruplex stabilization, ACS Appl Mater Interfaces (2020). https://doi.org/10.1021/acsomega.9b04221 .
Gui X, Luo F, Li Y, Zhou H, Qin Z, Liu Z, Gu J, Xie M, Zhao K, Dai B, Shin WS, He J, He L, Jiang L, Zhao M, Sun B, Li X, Liu C, Li D (2019) Structural basis for reversible amyloids of hnRNPA1 elucidates their role in stress granule assembly. Nat Commun . https://doi.org/10.1038/s41467-019-09902-7 .
Siomi H, Matunis MJ, Michael WM, Dreyfuss G (1993) The pre-mRNA binding K protein contains a novel evolutionary conserved motif. Nucleic Acids Res 21:1193–1198. https://doi.org/10.1093/nar/21.5.1193
doi: 10.1093/nar/21.5.1193
pubmed: 8464704
pmcid: 309281
Makeyev AV, Liebhaber SA (2002) The poly(C)-binding proteins: A multiplicity of functions and a search for mechanisms. RNA. 8:265–278. https://doi.org/10.1017/S1355838202024627
doi: 10.1017/S1355838202024627
pubmed: 12003487
pmcid: 1370249
Kiledjian M, Dreyfuss G (1992) Primary structure and binding activity of the hnRNP U protein: Binding RNA through RGG box. EMBO J 11:2655–2664. https://doi.org/10.1002/j.1460-2075.1992.tb05331.x
doi: 10.1002/j.1460-2075.1992.tb05331.x
pubmed: 1628625
pmcid: 556741
Dreyfuss G, Kim VN, Kataoka N (2002) Messenger-RNA-binding proteins and the messages they carry. Nat Rev Mol Cell Biol 3:195–205. https://doi.org/10.1038/nrm760
doi: 10.1038/nrm760
pubmed: 11994740
Chaudhury A, Chander P, Howe PH (2010) Heterogeneous nuclear ribonucleoproteins (hnRNPs) in cellular processes: Focus on hnRNP E1’s multifunctional regulatory roles. RNA. 16:1449–1462. https://doi.org/10.1261/rna.2254110
doi: 10.1261/rna.2254110
pubmed: 20584894
pmcid: 2905745
Geuens T, Bouhy D, Timmerman V (2016) The hnRNP family: Insights into their role in health and disease. Hum Genet 135:851–867. https://doi.org/10.1007/s00439-016-1683-5
doi: 10.1007/s00439-016-1683-5
pubmed: 27215579
pmcid: 4947485
Vance C, Scotter EL, Nishimura AL, Troakes C, Mitchell JC, Kathe C, Urwin H, Manser C et al (2013) ALS mutant FUS disrupts nuclear localization and sequesters wild-type FUS within cytoplasmic stress granules. Hum Mol Genet 22:2676–2688. https://doi.org/10.1093/hmg/ddt117
doi: 10.1093/hmg/ddt117
pubmed: 23474818
pmcid: 3674807
Hutchins EJ, Belrose JL, Szaro BG (2016) A novel role for the nuclear localization signal in regulating hnRNP K protein stability in vivo. Biochem Biophys Res Commun 478:772–776. https://doi.org/10.1016/j.bbrc.2016.08.023
doi: 10.1016/j.bbrc.2016.08.023
pubmed: 27501755
Hay DC, Kemp GD, Dargemont C, Hay RT (2001) Interaction between hnRNPA1 and IkappaBalpha is required for maximal activation of NF-kappaB-dependent transcription. Mol Cell Biol 21:3482–3490. https://doi.org/10.1128/MCB.21.10.3482-3490.2001
doi: 10.1128/MCB.21.10.3482-3490.2001
pubmed: 11313474
pmcid: 100270
Takimoto M, Tomonaga T, Matunis M, Avigan M, Krutzsch H, Dreyfuss G, Levens D (1993) Specific binding of heterogeneous ribonucleoprotein particle protein K to the human c-myc promoter, in vitro. J Biol Chem 268:18249–18258
doi: 10.1016/S0021-9258(17)46837-2
Tomonaga T, Levens D (1995) Heterogeneous nuclear ribonucleoprotein K is a DNA-binding transactivator. J Biol Chem 270:4875–4881. https://doi.org/10.1074/jbc.270.9.4875
doi: 10.1074/jbc.270.9.4875
pubmed: 7876260
Lynch M, Chen L, Ravitz MJ, Mehtani S, Korenblat K, Pazin MJ, Schmidt EV (2005) hnRNP K binds a core polypyrimidine element in the eukaryotic translation initiation factor 4E (eIF4E) promoter, and its regulation of eIF4E contributes to neoplastic transformation. Mol Cell Biol 25:6436–6453. https://doi.org/10.1128/MCB.25.15.6436-6453.2005
doi: 10.1128/MCB.25.15.6436-6453.2005
pubmed: 16024782
pmcid: 1190351
Michelotti EF, Michelotti GA, Aronsohn AI, Levens D (1996) Heterogeneous nuclear ribonucleoprotein K is a transcription factor. Mol Cell Biol 16:2350–2360. https://doi.org/10.1074/jbc.270.9.4875
doi: 10.1074/jbc.270.9.4875
pubmed: 8628302
pmcid: 231223
Denisenko ON, O’Neill B, Ostrowski J, Van Seuningen I, Bomsztyk K (1996) Zik1, a transcriptional repressor that interacts with the heterogeneous nuclear ribonucleoprotein particle K protein. J Biol Chem 271:27701–27706. https://doi.org/10.1074/jbc.271.44.27701
doi: 10.1074/jbc.271.44.27701
pubmed: 8910362
Graveley BR (2001) Alternative splicing: Increasing diversity in the proteomic world. Trends Genet 17:100–107. https://doi.org/10.1016/S0168-9525(00)02176-4
doi: 10.1016/S0168-9525(00)02176-4
pubmed: 11173120
Yeo G, Holste D, Kreiman G, Burge CB (2004) Variation in alternative splicing across human tissues. Genome Biol 5:R74. https://doi.org/10.1186/gb-2004-5-10-r74
doi: 10.1186/gb-2004-5-10-r74
pubmed: 15461793
pmcid: 545594
Conlon EG, Manley JL (2017) RNA-binding proteins in neurodegeneration: Mechanisms in aggregate. Genes Dev 31:1509–1528. https://doi.org/10.1101/gad.304055.117
doi: 10.1101/gad.304055.117
pubmed: 28912172
pmcid: 5630017
Huang H, Zhang J, Harvey SE, Hu X, Cheng C (2017) RNA G-quadruplex secondary structure promotes alternative splicing via the RNA-binding protein hnRNPF. Genes Dev 31:2296–2309. https://doi.org/10.1101/gad.305862.117
doi: 10.1101/gad.305862.117
pubmed: 29269483
pmcid: 5769772
Grabowski PJ, Black DL (2001) Alternative RNA splicing in the nervous system. Prog Neurobiol 65:289–308. https://doi.org/10.1016/S0301-0082(01)00007-7
doi: 10.1016/S0301-0082(01)00007-7
pubmed: 11473790
S. Gueroussov, R.J. Weatheritt, D. O’Hanlon, Z.Y. Lin, A. Narula, A.C. Gingras, B.J. Blencowe, Regulatory expansion in mammals of multivalent hnRNP assemblies that globally control alternative splicing, Cell. (2017). https://doi.org/10.1016/j.cell.2017.06.037 .
Martinez FJ, Pratt GA, Van Nostrand EL, Batra R, Huelga SC, Kapeli K, Freese P, Chun SJ, Ling K, Gelboin-Burkhart C, Fijany L, Wang HC, Nussbacher JK, Broski SM, Kim HJ, Lardelli R, Sundararaman B, Donohue JP, Javaherian A, Lykke-Andersen J, Finkbeiner S, Bennett CF, Ares M, Burge CB, Taylor JP, Rigo F, Yeo GW (2016) Protein-RNA networks regulated by normal and ALS-associated mutant HNRNPA2B1 in the nervous system, Neuron. https://doi.org/10.1016/j.neuron.2016.09.050 .
Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, König J, Hortobágyi T et al (2011) Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci. https://doi.org/10.1038/nn.2778
Black DL (2003) Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem. https://doi.org/10.1146/annurev.biochem.72.121801.161720
König J, Zarnack K, Rot G, Curk T, Kayikci M, Zupan B, Turner DJ, Luscombe NM et al (2010) ICLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat Struct Mol Biol. https://doi.org/10.1038/nsmb.1838
Xiao X, Wang Z, Jang M, Nutiu R, Wang ET, Burge CB (2009) Splice site strength-dependent activity and genetic buffering by poly-G runs. Nat Struct Mol Biol 16:1094–1100. https://doi.org/10.1038/nsmb.1661
doi: 10.1038/nsmb.1661
pubmed: 19749754
pmcid: 2766517
Tavanez J, Madl T, Kooshapur H, Sattler M, Valcárcel J (2012) HnRNP A1 proofreads 3′ splice site recognition by U2AF. Mol Cell 45:314–329. https://doi.org/10.1016/j.molcel.2011.11.033
doi: 10.1016/j.molcel.2011.11.033
pubmed: 22325350
Dewey CM, Cenik B, Sephton CF, Johnson BA, Herz J, Yu G (2012) TDP-43 aggregation in neurodegeneration: Are stress granules the key? Brain Res 1462:16–25. https://doi.org/10.1016/j.brainres.2012.02.032
doi: 10.1016/j.brainres.2012.02.032
pubmed: 22405725
pmcid: 3372581
Ash PEA, Vanderweyde TE, Youmans KL, Apicco DJ, Wolozin B (2014) Pathological stress granules in Alzheimer’s disease. Brain Res 1584:52–58. https://doi.org/10.1016/j.brainres.2014.05.052
doi: 10.1016/j.brainres.2014.05.052
pubmed: 25108040
pmcid: 4256948
Buchan JR, Parker R (2009) Eukaryotic stress granules: The ins and outs of translation. Mol Cell 36:932–941. https://doi.org/10.1016/j.molcel.2009.11.020
doi: 10.1016/j.molcel.2009.11.020
pubmed: 20064460
pmcid: 2813218
King OD, Gitler AD, Shorter J (2012) The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Res 1462:61–80. https://doi.org/10.1016/j.brainres.2012.01.016
doi: 10.1016/j.brainres.2012.01.016
pubmed: 22445064
pmcid: 3372647
Bowden HA, Dormann D (2016) Altered mRNP granule dynamics in FTLD pathogenesis. J Neurochem:112–133. https://doi.org/10.1111/jnc.13601
Guil S, Long JC, Caceres JF (2006) hnRNP A1 relocalization to the stress granules reflects a role in the stress response. Mol Cell Biol 26:5744–5758. https://doi.org/10.1128/MCB.00224-06
doi: 10.1128/MCB.00224-06
pubmed: 16847328
pmcid: 1592774
Kim WJ, Back SH, Kim V, Ryu I, Jang SK (2005) Sequestration of TRAF2 into stress granules interrupts tumor necrosis factor signaling under stress conditions. Mol Cell Biol 25:2450–2462. https://doi.org/10.1128/MCB.25.6.2450-2462.2005
doi: 10.1128/MCB.25.6.2450-2462.2005
pubmed: 15743837
pmcid: 1061607
Arimoto K, Fukuda H, Imajoh-Ohmi S, Saito H, Takekawa M (2008) Formation of stress granules inhibits apoptosis by suppressing stress-responsive MAPK pathways. Nat Cell Biol 10:1324–1332. https://doi.org/10.1038/ncb1791
doi: 10.1038/ncb1791
pubmed: 18836437
Takahara T, Maeda T (2012) Transient sequestration of TORC1 into stress granules during heat stress. Mol Cell 47:242–252. https://doi.org/10.1016/j.molcel.2012.05.019
doi: 10.1016/j.molcel.2012.05.019
pubmed: 22727621
Lagier-Tourenne C, Polymenidou M, Hutt KR, Vu AQ, Baughn M, Huelga SC, Clutario KM, Ling SC et al (2012) Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. Nat Neurosci 15:1488–1497. https://doi.org/10.1038/nn.3230
doi: 10.1038/nn.3230
pubmed: 23023293
pmcid: 3586380
Schmidt HB, Rohatgi R (2016) In vivo formation of vacuolated multi-phase compartments lacking membranes. Cell Rep. https://doi.org/10.1016/j.celrep.2016.06.088
Taylor JP, Brown RH, Cleveland DW (2016) Decoding ALS: From genes to mechanism. Nature. 539:197–206. https://doi.org/10.1038/nature20413
doi: 10.1038/nature20413
pubmed: 27830784
pmcid: 5585017
Hondele M, Heinrich S, Rios P. De Los, Weis K (2020) Membraneless organelles: phasing out of equilibrium, Emerg. Top Life Sci. ETLS201901. doi: https://doi.org/10.1042/ETLS20190190 .
Y.G. Zhao, H. Zhang, Phase separation in membrane biology: the interplay between membrane-bound organelles and membraneless condensates., Dev. Cell. (2020). https://doi.org/10.1016/j.devcel.2020.06.033 .
de Oliveira GAP, Cordeiro Y, Silva JL, Vieira TCRG (2019) Liquid-liquid phase transitions and amyloid aggregation in proteins related to cancer and neurodegenerative diseases, Adv. Protein Chem. Struct. Biol. https://doi.org/10.1016/bs.apcsb.2019.08.002 .
Lanni C, Racchi M, Memo M, Govoni S, Uberti D (2012) P53 at the crossroads between cancer and neurodegeneration. Free Radic Biol Med 52:1727–1733. https://doi.org/10.1016/j.freeradbiomed.2012.02.034
doi: 10.1016/j.freeradbiomed.2012.02.034
pubmed: 22387179
Zhang Q, Guo S, Zhang X, Tang S, Shao W, Han X, Wang L, Du Y (2015) Inverse relationship between cancer and Alzheimer’s disease: A systemic review meta-analysis. Neurol Sci 36:1987–1994. https://doi.org/10.1007/s10072-015-2282-2
doi: 10.1007/s10072-015-2282-2
pubmed: 26248482
Yang Y, Geldmacher DS, Herrup K (2001) DNA replication precedes neuronal cell death in Alzheimer’s disease. J Neurosci 21:2661–2668
doi: 10.1523/JNEUROSCI.21-08-02661.2001
Yurov YB, Vorsanova SG, Iourov IY (2011) The DNA replication stress hypothesis of Alzheimer’s disease. Sci World J 11:2602–2612. https://doi.org/10.1100/2011/625690
doi: 10.1100/2011/625690
Weaver BAA, Cleveland DW (2005) Decoding the links between mitosis, cancer, and chemotherapy: The mitotic checkpoint, adaptation, and cell death. Cancer Cell 8:7–12. https://doi.org/10.1016/j.ccr.2005.06.011
doi: 10.1016/j.ccr.2005.06.011
pubmed: 16023594
Ding J, Hayashi MK, Zhang Y, Manche L, Krainer AR, Xu RM (1999) Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA. Genes Dev 13:1102–1115. https://doi.org/10.1101/gad.13.9.1102
doi: 10.1101/gad.13.9.1102
pubmed: 10323862
pmcid: 316951
LaBranche H, Dupuis S, Ben-David Y, Bani MR, Wellinger RJ, Chabot B (1998) Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase. Nat Genet 19:199–202. https://doi.org/10.1038/575
doi: 10.1038/575
pubmed: 9620782
Grandori C, Cowley SM, James LP, Eisenman RN (2000) The Myc/max/mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol 16:653–699. https://doi.org/10.1146/annurev.cellbio.16.1.653
doi: 10.1146/annurev.cellbio.16.1.653
pubmed: 11031250
Chevalier-Larsen E, Holzbaur EL (2006) Axonal transport and neurodegenerative disease. Biochim Biophys Acta 1762:1094–1108. https://doi.org/10.1016/j.bbadis.2006.04.002
doi: 10.1016/j.bbadis.2006.04.002
pubmed: 16730956
Morfini GA, Burns M, Binder LI, Kanaan NM, LaPointe N, Bosco DA, Brown RH, Brown H et al (2009) Axonal transport defects in neurodegenerative diseases. J Neurosci 29:12776–12786. https://doi.org/10.1523/JNEUROSCI.3463-09.2009
doi: 10.1523/JNEUROSCI.3463-09.2009
pubmed: 19828789
pmcid: 2801051
Millecamps S, Julien JP (2013) Axonal transport deficits and neurodegenerative diseases. Nat Rev Neurosci 14:161–176. https://doi.org/10.1038/nrn3380
doi: 10.1038/nrn3380
pubmed: 23361386
Hares K, WIlkins A (2017) Axonal transport proteins as biomarkers of neurodegeneration? Biomark Med 11:589–591
doi: 10.2217/bmm-2017-0163
von Kügelgen N, Chekulaeva M (2020) Conservation of a core neurite transcriptome across neuronal types and species, Wiley Interdiscip. Rev. RNA. e1590
Glinka M, Herrmann T, Funk N, Havlicek S, Rossoll W, Winkler C, Sendtner M (2010) The heterogeneous nuclear ribonucleoprotein-R is necessary for axonal β-actin mRNA translocation in spinal motor neurons. Hum Mol Genet 19:1951–1966. https://doi.org/10.1093/hmg/ddq073
doi: 10.1093/hmg/ddq073
pubmed: 20167579
Briese M, Saal-Bauernschubert L, Ji C, Moradi M, Ghanawi H, Uhl M, Appenzeller S, Backofen R, Sendtner M (2018) hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons., PNAS. Published
Liu Y, Szaro BG (2011) hnRNP K post-transcriptionally co-regulates multiple cytoskeletal genes needed for axonogenesis. Development 138:3079–3090. https://doi.org/10.1242/dev.066993
doi: 10.1242/dev.066993
pubmed: 21693523
Koppers M, Cagnetta R, Shigeoka T, Wunderlich LC, Vallejo-Ramirez P, Lin JQ, Zhao S, Jakobs MA, Dwivedy A, Minett MS, Bellon A, Kaminski CF, Harris WA, Flanagan JG, Holt CE (2019) Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons, Elife. 8
Pushpalatha KV, Besse F (2019) Local translation in axons: When membraneless RNP granules meet membrane-bound organelles. Front Mol Biosci 6:129
doi: 10.3389/fmolb.2019.00129
Lee SJ, Oses-Prieto JA, Kawaguchi R, Sahoo PK, Kar AN, Rozenbaum M, Oliver D, Chand S et al (2018) hnRNPs interacting with mRNA localization motifs define axonal RNA regulons. Mol Cell Proteomics 17:2091–2106
doi: 10.1074/mcp.RA118.000603
Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133. https://doi.org/10.1126/science.1134108
doi: 10.1126/science.1134108
pubmed: 17023659
Neumann M, Kwong LK, Sampathu DM, Trojanowski JQ, Lee VMY (2007) TDP-43 proteinopathy in frontotemporal lobar degeneration and amyotrophic lateral sclerosis: Protein misfolding diseases without amyloidosis. Arch Neurol 64:1388–1394. https://doi.org/10.1001/archneur.64.10.1388
doi: 10.1001/archneur.64.10.1388
pubmed: 17923623
DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NCA et al (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72:245–256. https://doi.org/10.1016/j.neuron.2011.09.011
doi: 10.1016/j.neuron.2011.09.011
pubmed: 21944778
pmcid: 3202986
Renoux AJ, Todd PK (2012) Neurodegeneration the RNA way. Prog Neurobiol 97:173–189. https://doi.org/10.1016/j.pneurobio.2011.10.006
doi: 10.1016/j.pneurobio.2011.10.006
pubmed: 22079416
Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C et al (1995) Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 80:155–165. https://doi.org/10.1016/0092-8674(95)90460-3
doi: 10.1016/0092-8674(95)90460-3
pubmed: 7813012
Lorson CL, Hahnen E, Androphy EJ, Wirth B (1999) A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci 96:6307–6311. https://doi.org/10.1073/pnas.96.11.6307
doi: 10.1073/pnas.96.11.6307
pubmed: 10339583
Hua Y, Vickers TA, Okunola HL, Bennett CF, Krainer AR (2008) Antisense masking of an hnRNP A1/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice. Am J Hum Genet 82:834–848. https://doi.org/10.1016/j.ajhg.2008.01.014
doi: 10.1016/j.ajhg.2008.01.014
pubmed: 18371932
pmcid: 2427210
Hofmann Y, Wirth B (2002) hnRNP-G promotes exon 7 inclusion of survival motor neuron (SMN) via direct interaction with Htra2-beta1. Hum Mol Genet 11:2037–2049. https://doi.org/10.1093/hmg/11.17.2037
doi: 10.1093/hmg/11.17.2037
pubmed: 12165565
Moursy A, Allain FHT, Cléry A (2014) Characterization of the RNA recognition mode of hnRNP G extends its role in SMN2 splicing regulation. Nucleic Acids Res 42:6659–6672. https://doi.org/10.1093/nar/gku244
doi: 10.1093/nar/gku244
pubmed: 24692659
pmcid: 4041419
Chen H-H, Chang J-G, Lu R-M, Peng T-Y, Tarn W-Y (2008) The RNA binding protein hnRNP Q modulates the utilization of exon 7 in the survival motor neuron 2 (SMN2) Gene. Mol Cell Biol 28:6929–6938. https://doi.org/10.1128/MCB.01332-08
doi: 10.1128/MCB.01332-08
pubmed: 18794368
pmcid: 2573304
Cho S, Moon H, Loh TJ, Oh HK, Cho S, Choy HE, Song WK, Chun JS et al (2014) HnRNP M facilitates exon 7 inclusion of SMN2 pre-mRNA in spinal muscular atrophy by targeting an enhancer on exon 7. Biochim Biophys Acta - Gene Regul Mech 1839:306–315. https://doi.org/10.1016/j.bbagrm.2014.02.006
doi: 10.1016/j.bbagrm.2014.02.006
Kashima T, Manley JL (2003) A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy. Nat Genet 34:460–463. https://doi.org/10.1038/ng1207
doi: 10.1038/ng1207
pubmed: 12833158
Kashima T, Rao N, David CJ, Manley JI (2007) hnRNP A1 functions with specificity in repression of SMN2 exon 7 splicing. Hum Mol Genet 16:3149–3159. https://doi.org/10.1093/hmg/ddm276
doi: 10.1093/hmg/ddm276
pubmed: 17884807
Koed Doktor T, Schroeder LD, Vested A, Palmfeldt J, Andersen HS, Gregersen N, Andresen BS (2011) SMN2 exon 7 splicing is inhibited by binding of hnRNP A1 to a common ESS motif that spans the 3′ splice site. Hum Mutat 32:220–230. https://doi.org/10.1002/humu.21419
doi: 10.1002/humu.21419
Baek J, Jeong H, Ham Y, Jo YH, Choi M, Kang M, Son B, Choi S, Ryu HW, Kim J, Shen H, Sydara K, Lee SW, Kim SY, Han SB, Oh SR, Cho S (2019) Improvement of spinal muscular atrophy via correction of the SMN2 splicing defect by Brucea javanica (L.) Merr. extract and Bruceine D, Phytomedicine. https://doi.org/10.1016/j.phymed.2019.153089 .
Beusch I, Barraud P, Moursy A, Cléry A, Allain FHT (2017) Tandem hnRNP A1 RNA recognition motifs act in concert to repress the splicing of survival motor neuron exon 7, Elife. 6. https://doi.org/10.7554/eLife.25736 .
Ruiz R, Casañas JJ, Torres-Benito L, Cano R, Tabares L (2010) Altered intracellular Ca2+ homeostasis in nerve terminals of severe spinal muscular atrophy mice. J Neurosci 30:849–857. https://doi.org/10.1523/JNEUROSCI.4496-09.2010
doi: 10.1523/JNEUROSCI.4496-09.2010
pubmed: 20089893
pmcid: 6633088
Kariya S, Obis T, Garone C, Akay T, Sera F, Iwata S, Homma S, Monani UR (2014) Requirement of enhanced survival motoneuron protein imposed during neuromuscular junction maturation. J Clin Invest 124:785–800. https://doi.org/10.1172/JCI72017
doi: 10.1172/JCI72017
pubmed: 24463453
pmcid: 3904626
Rossoll W, Kröning A-K, Ohndorf U-M, Steegborn C, Jablonka S, Sendtner M (2002) Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: A role for Smn in RNA processing in motor axons? Hum Mol Genet 11:93–105. https://doi.org/10.1093/hmg/11.1.93
doi: 10.1093/hmg/11.1.93
pubmed: 11773003
Dombert B, Sivadasan R, Simon CM, Jablonka S, Sendtner M (2014) Presynaptic localization of SMN and hnRNP R in axon terminals of embryonic and postnatal mouse motoneurons. PLoS One. 9. https://doi.org/10.1371/journal.pone.0110846 .
De Vos KJ, Grierson AJ, Ackerley S, Miller CCJ (2008) Role of axonal transport in neurodegenerative diseases. Annu Rev Neurosci 31:151–173. https://doi.org/10.1146/annurev.neuro.31.061307.090711
doi: 10.1146/annurev.neuro.31.061307.090711
pubmed: 18558852
Rossoll W, Jablonka S, Andreassi C, Kröning AK, Karle K, Monani UR, Sendtner M (2003) Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of β-actin mRNA in growth cones of motoneurons. J Cell Biol 163:801–812. https://doi.org/10.1083/jcb.200304128
doi: 10.1083/jcb.200304128
pubmed: 14623865
pmcid: 2173668
Bennett Frank C, Krainer AR, Cleveland DW (2019) Antisense oligonucleotide therapies for neurodegenerative diseases. Annu Rev Neurosci. https://doi.org/10.1146/annurev-neuro-070918-050501
Mercuri E, Darras BT, Chiriboga CA, Day JW, Campbell C, Connolly AM, Iannaccone ST, Kirschner J et al (2018) Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. https://doi.org/10.1056/NEJMoa1710504
Chiriboga CA, Swoboda KJ, Darras BT, Iannaccone ST, Montes J, De Vivo DC, Norris DA, Bennett CF, Bishop KM (2016) Results from a phase 1 study of nusinersen (ISIS-SMN Rx) in children with spinal muscular atrophy, Neurology. https://doi.org/10.1212/WNL.0000000000002445 .
Donev R, Newall A, Thome J, Sheer D (2007) A role for SC35 and hnRNPA1 in the determination of amyloid precursor protein isoforms. Mol Psychiatry 12:681–690. https://doi.org/10.1038/sj.mp.4001971
doi: 10.1038/sj.mp.4001971
pubmed: 17353911
pmcid: 2684093
Bekenstein U, Soreq H (2013) Heterogeneous nuclear ribonucleoprotein A1 in health and neurodegenerative disease: From structural insights to post-transcriptional regulatory roles. Mol Cell Neurosci 56:436–446. https://doi.org/10.1016/j.mcn.2012.12.002
doi: 10.1016/j.mcn.2012.12.002
pubmed: 23247072
Berson A, Barbash S, Shaltiel G, Goll Y, Hanin G, Greenberg DS, Ketzef M, Becker AJ et al (2012) Cholinergic-associated loss of hnRNP-A/B in Alzheimer’s disease impairs cortical splicing and cognitive function in mice. EMBO Mol Med 4:730–742. https://doi.org/10.1002/emmm.201100995
doi: 10.1002/emmm.201100995
pubmed: 22628224
pmcid: 3494073
Liu XY, Li HL, Bin Su J, Ding FH, Zhao JJ, Chai F, Li YX, Cui SC et al (2015) Regulation of RAGE splicing by hnRNP A1 and Tra2β-1 and its potential role in AD pathogenesis. J Neurochem 133:187–198. https://doi.org/10.1111/jnc.13069
doi: 10.1111/jnc.13069
pubmed: 25689357
Villa C, Fenoglio C, De Riz M, Clerici F, Marcone A, Benussi L, Ghidoni R, Gallone S et al (2011) Role of hnRNP-A1 and miR-590-3p in neuronal death: Genetics and expression analysis in patients with Alzheimer disease and frontotemporal lobar degeneration. Rejuvenation Res 14:275–281. https://doi.org/10.1089/rej.2010.1123
doi: 10.1089/rej.2010.1123
pubmed: 21548758
Jarrett JT, Lansbury PT (1993) Seeding “one-dimensional crystallization” of amyloid: A pathogenic mechanism in Alzheimer’s disease and scrapie? Cell. 73:1055–1058. https://doi.org/10.1016/0092-8674(93)90635-4
doi: 10.1016/0092-8674(93)90635-4
pubmed: 8513491
Goedert M, Clavaguera F, Tolnay M (2010) The propagation of prion-like protein inclusions in neurodegenerative diseases. Trends Neurosci 33:317–325. https://doi.org/10.1016/j.tins.2010.04.003
doi: 10.1016/j.tins.2010.04.003
pubmed: 20493564
Frost B, Diamond MI (2010) Prion-like mechanisms in neurodegenerative diseases. Nat Rev Neurosci 11:155–159. https://doi.org/10.1038/nrn2786
doi: 10.1038/nrn2786
pubmed: 20029438
Brundin P, Melki R, Kopito R (2010) Prion-like transmission of protein aggregates in neurodegenerative diseases. Nat Rev Mol Cell Biol 11:301–307. https://doi.org/10.1038/nrm2873
doi: 10.1038/nrm2873
pubmed: 20308987
pmcid: 2892479
Zearfoss NR, Johnson ES, Ryder SP (2013) hnRNP A1 and secondary structure coordinate alternative splicing of mag. RNA 19:948–957. https://doi.org/10.1261/rna.036780.112
doi: 10.1261/rna.036780.112
pubmed: 23704325
pmcid: 3683929
Jean-Philippe J, Paz S, Caputi M (2013) hnRNP A1: The Swiss Army knife of gene expression. Int J Mol Sci 14:18999–19024. https://doi.org/10.3390/ijms140918999
doi: 10.3390/ijms140918999
pubmed: 24065100
pmcid: 3794818
Lee EK, Kim HH, Kuwano Y, Abdelmohsen K, Srikantan S, Subaran SS, Gleichmann M, Mughal MR et al (2010) HnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies. Nat Struct Mol Biol 17:732–739. https://doi.org/10.1038/nsmb.1815
doi: 10.1038/nsmb.1815
pubmed: 20473314
pmcid: 2908492
Rajagopalan LE, Westmark CJ, Jarzembowski JA, Malter JS (1998) HnRNP C increases amyloid precursor protein (APP) production by stabilizing APP mRNA. Nucleic Acids Res 26:3418–3423. https://doi.org/10.1093/nar/26.14.3418
doi: 10.1093/nar/26.14.3418
pubmed: 9649628
pmcid: 147701
Rivera D, Fedele E, Marinari UM, Pronzato MA, Ricciarelli R (2015) Evaluating the role of hnRNP-C and FMRP in the cAMP-induced APP metabolism. BioFactors. 41:121–126. https://doi.org/10.1002/biof.1207
doi: 10.1002/biof.1207
pubmed: 25809670
Mizukami K, Ishikawa M, Iwakiri M, Ikonomovic MD, Dekosky ST, Kamma H, Asada T (2005) Immunohistochemical study of the hnRNP A2 and B1 in the hippocampal formations of brains with Alzheimer’s disease. Neurosci Lett 386:111–115. https://doi.org/10.1016/j.neulet.2005.05.070
doi: 10.1016/j.neulet.2005.05.070
pubmed: 15993539
Ishikawa M, Mizukami K, Iwakiri M, Kamma H, Ikonomovic MD, Dekosky ST, Asada T (2004) Immunohistochemical study of hnRNP B1 in the postmortem temporal cortices of patients with Alzheimer’s disease. Neurosci Res 50:481–484. https://doi.org/10.1016/j.neures.2004.08.013
doi: 10.1016/j.neures.2004.08.013
pubmed: 15567486
Ashraf GM, Ganash M, Athanasios A (2019) Computational analysis of non-coding RNAs in Alzheimer’s disease. Bioinformation. https://doi.org/10.6026/97320630015351 .
Herrup K (2004) Divide and die: Cell cycle events as triggers of nerve cell death. J Neurosci 24:9232–9239. https://doi.org/10.1523/JNEUROSCI.3347-04.2004
doi: 10.1523/JNEUROSCI.3347-04.2004
pubmed: 15496657
pmcid: 6730083
Lee SW, Lee MH, Park JH, Kang SH, Yoo HM, Ka SH, Oh YM, Jeon YJ et al (2012) SUMOylation of hnRNP-K is required for p53-mediated cell-cycle arrest in response to DNA damage. EMBO J 31:4441–4452. https://doi.org/10.1038/emboj.2012.293
doi: 10.1038/emboj.2012.293
pubmed: 23092970
pmcid: 3512394
Yang F, Yi F, Han X, Du Q, Liang Z (2013) MALAT-1 interacts with hnRNP C in cell cycle regulation. FEBS Lett 587:3175–3181. https://doi.org/10.1016/j.febslet.2013.07.048
doi: 10.1016/j.febslet.2013.07.048
pubmed: 23973260
Moumen A, Masterson P, O’Connor MJ, Jackson SP (2005) hnRNP K: An HDM2 target and transcriptional coactivator of p53 in response to DNA damage. Cell 123:1065–1078. https://doi.org/10.1016/j.cell.2005.09.032
doi: 10.1016/j.cell.2005.09.032
pubmed: 16360036
Mecocci P, MacGarvey U, Beal MF (1994) Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease. Ann Neurol 36:747–751. https://doi.org/10.1002/ana.410360510
doi: 10.1002/ana.410360510
pubmed: 7979220
Kitamura Y, Shimohama S, Kamoshima W, Matsuoka Y, Nomura Y, Taniguchi T (1997) Changes of p53 in the brains of patients with Alzheimer’s disease. Biochem Biophys Res Commun 232:418–421. https://doi.org/10.1006/bbrc.1997.6301
doi: 10.1006/bbrc.1997.6301
pubmed: 9125193
Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, Burrell JR, Zoing MC (2011) Amyotrophic lateral sclerosis, 942–955. Lancet 377. https://doi.org/10.1016/S0140-6736(10)61156-7
McKhann GM, Albert MS, Grossman M, Miller B, Dickson D, Trojanowski JQ (2001) Clinical and pathological diagnosis of frontotemporal dementia: Report of the work group on Frontotemporal dementia and Pick’s disease. Arch Neurol 58:1803–1809. https://doi.org/10.1001/archneur.58.11.1803
doi: 10.1001/archneur.58.11.1803
pubmed: 11708987
Boylan K (2015) Familial amyotrophic lateral sclerosis. Neurol Clin. https://doi.org/10.1016/j.ncl.2015.07.001
Lashley T, Rohrer JD, Mead S, Revesz T (2015) Review: An update on clinical, genetic and pathological aspects of frontotemporal lobar degenerations. Neuropathol Appl Neurobiol. https://doi.org/10.1111/nan.12250
Ayala YM, Zago P, D’Ambrogio A, Xu YF, Petrucelli L, Buratti E, Baralle FE (2008) Structural determinants of the cellular localization and shuttling of TDP-43. J Cell Sci. https://doi.org/10.1242/jcs.038950
Buratti E, Baralle FE (2010) The multiple roles of TDP-43 in pre-mRNA processing and gene expression regulation. RNA Biol. https://doi.org/10.4161/rna.7.4.12205 .
Ratti A, Buratti E (2016) Physiological functions and pathobiology of TDP-43 and FUS/TLS proteins. J Neurochem. https://doi.org/10.1111/jnc.13625
Buratti E, Brindisi A, Giombi M, Tisminetzky S, Ayala YM, Baralle FE (2005) TDP-43 binds heterogeneous nuclear ribonucleoprotein a/B through its C-terminal tail: An important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing. J Biol Chem 280:37572–37584. https://doi.org/10.1074/jbc.M505557200
doi: 10.1074/jbc.M505557200
pubmed: 16157593
Ash PEA, Zhang YJ, Roberts CM, Saldi T, Hutter H, Buratti E, Petrucelli L, Link CD (2010) Neurotoxic effects of TDP-43 overexpression in C. elegans. Hum Mol Genet. https://doi.org/10.1093/hmg/ddq230 .
Kabashi E, Lin L, Tradewell ML, Dion PA, Bercier V, Bourgouin P, Rochefort D, Bel Hadj S, Durham HD, Vande Velde C, Rouleau GA, Drapeau P (2009) Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo. Hum Mol Genet. https://doi.org/10.1093/hmg/ddp534 .
Liachko NF, Guthrie CR, Kraemer BC (2010) Phosphorylation promotes neurotoxicity in a Caenorhabditis elegans model of TDP-43 proteinopathy. J Neurosci. https://doi.org/10.1523/JNEUROSCI.2911-10.2010 .
Stallings NR, Puttaparthi K, Luther CM, Burns DK, Elliott JL (2010) Progressive motor weakness in transgenic mice expressing human TDP-43. Neurobiol Dis. https://doi.org/10.1016/j.nbd.2010.06.017
Wils H, Kleinberger G, Janssens J, Pereson S, Joris G, Cuijt I, Smits V, Ceuterick-De Groote C et al (2010) TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci U S A. https://doi.org/10.1073/pnas.0912417107
Xu YF, Zhang YJ, Lin WL, Cao X, Stetler C, Dickson DW, Lewis J, Petrucelli L (2011) Expression of mutant TDP-43 induces neuronal dysfunction in transgenic mice. Mol Neurodegener. https://doi.org/10.1186/1750-1326-6-73 .
Highley JR, Kirby J, Jansweijer JA, Webb PS, Hewamadduma CA, Heath PR, Higginbottom A, Raman R, Ferraiuolo L, Cooper-Knock J, Mcdermott CJ, Wharton SB, Shaw PJ, Ince PG (2014) Loss of nuclear TDP-43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurones. Neuropathol Appl Neurobiol. https://doi.org/10.1111/nan.12148 .
Colombrita C, Onesto E, Buratti E, de la Grange P, Gumina V, Baralle FE, Silani V, Ratti A (2015) From transcriptomic to protein level changes in TDP-43 and FUS loss-of-function cell models. Biochim Biophys Acta - Gene Regul Mech. https://doi.org/10.1016/j.bbagrm.2015.10.015 .
Klim JR, Williams LA, Limone F, Guerra San Juan I, Davis-Dusenbery BN, Mordes DA, Burberry A, Steinbaugh MJ, Gamage KK, Kirchner R, Moccia R, Cassel SH, Chen K, Wainger BJ, Woolf CJ, Eggan K (2019) ALS-implicated protein TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair. Nat Neurosci. https://doi.org/10.1038/s41593-018-0300-4 .
Mori K, Lammich S, Mackenzie IRA, Forné I, Zilow S, Kretzschmar H, Edbauer D, Janssens J et al (2013) HnRNP A3 binds to GGGGCC repeats and is a constituent of p62-positive/TDP43-negative inclusions in the hippocampus of patients with C9orf72 mutations. Acta Neuropathol 125:413–423. https://doi.org/10.1007/s00401-013-1088-7
doi: 10.1007/s00401-013-1088-7
pubmed: 23381195
Lee YB, Chen HJ, Peres JN, Gomez-Deza J, Attig J, Štalekar M, Troakes C, Nishimura AL et al (2013) Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic. Cell Rep 5:1178–1186. https://doi.org/10.1016/j.celrep.2013.10.049
doi: 10.1016/j.celrep.2013.10.049
pubmed: 24290757
pmcid: 3898469
Haeusler AR, Donnelly CJ, Periz G, Simko EAJ, Shaw PG, Kim MS, Maragakis NJ, Troncoso JC et al (2014) C9orf72 nucleotide repeat structures initiate molecular cascades of disease. Nature. 507:195–200. https://doi.org/10.1038/nature13124
doi: 10.1038/nature13124
pubmed: 24598541
pmcid: 4046618
Nahalka J (2019) The role of the protein–RNA recognition code in neurodegeneration, Cell Mol Life Sci. https://doi.org/10.1007/s00018-019-03096-3 .
Conlon EG, Lu L, Sharma A, Yamazaki T, Tang T, Shneider NA, Manley JL (2016) The C9ORF72 GGGGCC expansion forms RNA G-quadruplex inclusions and sequesters hnRNP H to disrupt splicing in ALS brains. Elife. 5. https://doi.org/10.7554/eLife.17820 .
Freibaum BD, Chitta RK, High AA, Taylor JP (2010) Global analysis of TDP-43 interacting proteins reveals strong association with RNA splicing and translation machinery. J Proteome Res 9:1104–1120. https://doi.org/10.1021/pr901076y
doi: 10.1021/pr901076y
pubmed: 20020773
pmcid: 2897173
Moujalled D, James JL, Yang S, Zhang K, Duncan C, Moujalled DM, Parker SJ, Caragounis A et al (2015) Phosphorylation of hnRNP K by cyclin-dependent kinase 2 controls cytosolic accumulation of TDP-43. Hum Mol Genet 24:1655–1669. https://doi.org/10.1093/hmg/ddu578
doi: 10.1093/hmg/ddu578
pubmed: 25410660
Lee KH, Zhang P, Kim HJ, Mitrea DM, Sarkar M, Freibaum BD, Cika J, Coughlin M, Messing J, Molliex A, Maxwell BA, Kim NC, Temirov J, Moore J, Kolaitis RM, Shaw TI, Bai B, Peng J, Kriwacki RW, Taylor JP (2016) C9orf72 dipeptide repeats impair the assembly, dynamics, and function of membrane-less organelles, cell. https://doi.org/10.1016/j.cell.2016.10.002 .
Wen X, Tan W, Westergard T, Krishnamurthy K, Markandaiah SS, Shi Y, Lin S, Shneider NA, Monaghan J, Pandey UB, Pasinelli P, Ichida JK, Trotti D (2014) Antisense proline-arginine RAN dipeptides linked to C9ORF72-ALS/FTD form toxic nuclear aggregates that initiate invitro and invivo neuronal death, neuron. https://doi.org/10.1016/j.neuron.2014.12.010 .
Balendra R, Isaacs AM (2018) C9orf72-mediated ALS and FTD: Multiple pathways to disease. Nat Rev Neurol. https://doi.org/10.1038/s41582-018-0047-2 .
Leko MB, Župunski V, Kirincich J, Smilović D, Hortobágyi T, Hof PR, Šimić G (2019) Molecular mechanisms of neurodegeneration related to C9orf72 hexanucleotide repeat expansion. Behav Neurol. https://doi.org/10.1155/2019/2909168
Jovičić A, Paul JW, Gitler AD (2016) Nuclear transport dysfunction: A common theme in amyotrophic lateral sclerosis and frontotemporal dementia. J Neurochem:134–144. https://doi.org/10.1111/jnc.13642
Liu Q, Shu S, Wang RR, Liu F, Cui B, Guo XN, Lu CX, Li XG et al (2016) Whole-exome sequencing identifies a missense mutation in hnRNPA1 in a family with flail arm ALS. Neurology. 87:1763–1769. https://doi.org/10.1212/WNL.0000000000003256
doi: 10.1212/WNL.0000000000003256
pubmed: 27694260
Honda H, Hamasaki H, Wakamiya T, Koyama S, Suzuki SO, Fujii N, Iwaki T (2015) Loss of hnRNPA1 in ALS spinal cord motor neurons with TDP-43-positive inclusions. Neuropathology. 35:37–43. https://doi.org/10.1111/neup.12153
doi: 10.1111/neup.12153
pubmed: 25338872
Davidson YS, Robinson AC, Flood L, Rollinson S, Benson BC, Asi YT, Richardson A, Jones M et al (2017) Heterogeneous ribonuclear protein E2 (hnRNP E2) is associated with TDP-43-immunoreactive neurites in semantic dementia but not with other TDP-43 pathological subtypes of Frontotemporal lobar degeneration. Acta Neuropathol Commun 5:54. https://doi.org/10.1186/s40478-017-0454-4
doi: 10.1186/s40478-017-0454-4
pubmed: 28666471
pmcid: 5493127
Gami-Patel P, Bandopadhyay R, Brelstaff J, Revesz T, Lashley T (2016) The presence of heterogeneous nuclear ribonucleoproteins in frontotemporal lobar degeneration with FUS-positive inclusions. Neurobiol Aging 46:192–203. https://doi.org/10.1016/j.neurobiolaging.2016.07.004
doi: 10.1016/j.neurobiolaging.2016.07.004
pubmed: 27500866
Gittings LM, Foti SC, Benson BC, Gami-Patel P, Isaacs AM, Lashley T (2019) Heterogeneous nuclear ribonucleoproteins R and Q accumulate in pathological inclusions in FTLD-FUS. Acta Neuropathol Commun. https://doi.org/10.1186/s40478-019-0673-y .
Maniecka Z, Polymenidou M (2015) From nucleation to widespread propagation: A prion-like concept for ALS. Virus Res 207:94–105. https://doi.org/10.1016/j.virusres.2014.12.032
doi: 10.1016/j.virusres.2014.12.032
pubmed: 25656065
Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B et al (2013) Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 495:467–473. https://doi.org/10.1038/nature11922
doi: 10.1038/nature11922
pubmed: 23455423
pmcid: 3756911
Steinman L (1996) Multiple sclerosis: A coordinated immunological attack against myelin in the central nervous system. Cell. 85:299–302. https://doi.org/10.1016/S0092-8674(00)81107-1
doi: 10.1016/S0092-8674(00)81107-1
pubmed: 8616884
Reindl M, Linington C, Brehm U, Egg R, Dilitz E, Deisenhammer F, Poewe W, Berger T (1999) Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: A comparative study. Brain. 122:2047–2056. https://doi.org/10.1093/brain/122.11.2047
doi: 10.1093/brain/122.11.2047
pubmed: 10545390
Levin MC, Lee S, Gardner LA, Shin Y, Douglas JN, Cooper C (2013) Autoantibodies to non-myelin antigens as contributors to the pathogenesis of multiple sclerosis. J Clin Cell Immunol. 4. https://doi.org/10.4172/2155-9899.1000148 .
Kamma H, Portman DS, Dreyfuss G (1995) Cell type-specific expression of hnRNP proteins. Exp Cell Res 221:187–196. https://doi.org/10.1006/excr.1995.1366
doi: 10.1006/excr.1995.1366
pubmed: 7589244
Kamma H, Horiguchi H, Wan L, Matsui M, Fujiwara M, Fujimoto M, Yazawa T, Dreyfuss G (1999) Molecular characterization of the hnRNP A2/B1 proteins: Tissue-specific expression and novel isoforms. Exp Cell Res 246:399–411. https://doi.org/10.1006/excr.1998.4323
doi: 10.1006/excr.1998.4323
pubmed: 9925756
Yukitake M, Sueoka E, Sueoka-Aragane N, Sato A, Ohashi H, Yakushiji Y, Saito M, Osame M et al (2008) Significantly increased antibody response to heterogeneous nuclear ribonucleoproteins in cerebrospinal fluid of multiple sclerosis patients but not in patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. J Neuro-Oncol 14:130–135. https://doi.org/10.1080/13550280701883840
doi: 10.1080/13550280701883840
Lee S, Xu L, Shin Y, Gardner L, Hartzes A, Dohan FC, Raine C, Homayouni R et al (2011) A potential link between autoimmunity and neurodegeneration in immune-mediated neurological disease. J Neuroimmunol 235:56–69. https://doi.org/10.1016/j.jneuroim.2011.02.007
doi: 10.1016/j.jneuroim.2011.02.007
pubmed: 21570130
Lee S, Levin M (2014) Novel somatic single nucleotide variants within the RNA binding protein hnRNP A1 in multiple sclerosis patients, F1000Research. https://doi.org/10.12688/f1000research.4436.2 .
Douglas JN (2013) Antibodies to an intracellular antigen penetrate neuronal cells and cause deleterious effects. J Clin Cell Immunol 04:1–7. https://doi.org/10.4172/2155-9899.1000134
doi: 10.4172/2155-9899.1000134
Sueoka E, Yukitake M, Iwanaga K, Sueoka N, Aihara T, Kuroda Y (2004) Autoantibodies against heterogeneous nuclear ribonucleoprotein B1 in CSF of MS patients. Ann Neurol 56:778–786. https://doi.org/10.1002/ana.20276
doi: 10.1002/ana.20276
pubmed: 15497154
Douglas JN, Gardner LA, Salapa HE, Lalor SJ, Lee S, Segal BM, Sawchenko PE, Levin MC (2016) Antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease. J. Neuroinflammation. 13. https://doi.org/10.1186/s12974-016-0647-y .
Saarela J, Kallio SP, Chen D, Montpetit A, Jokiaho A, Choi E, Asselta R, Bronnikov D et al (2006) PRKCA and multiple sclerosis: Association in two independent populations. PLoS Genet 2:0364–0375. https://doi.org/10.1371/journal.pgen.0020042
doi: 10.1371/journal.pgen.0020042
Paraboschi EM, Rimoldi V, Soldà G, Tabaglio T, Dall’Osso C, Saba E, Vigliano M, Salviati A et al (2014) Functional variations modulating PRKCA expression and alternative splicing predispose to multiple sclerosis. Hum Mol Genet 23:6746–6761. https://doi.org/10.1093/hmg/ddu392
doi: 10.1093/hmg/ddu392
pubmed: 25080502
Engel AG, Shen X-M, Selcen D, Sine SM (2015) Congenital myasthenic syndromes: Pathogenesis, diagnosis, and treatment. Lancet Neurol 14:420–434. https://doi.org/10.1016/S1474-4422(14)70201-7
doi: 10.1016/S1474-4422(14)70201-7
pubmed: 25792100
pmcid: 4520251
Ohno K, Rahman MA, Nazim M, Nasrin F, Lin Y, Takeda JI, Masuda A (2017) Splicing regulation and dysregulation of cholinergic genes expressed at the neuromuscular junction. J Neurochem 142:64–72. https://doi.org/10.1111/jnc.13954
doi: 10.1111/jnc.13954
pubmed: 28072465
Masuda A, Shen XM, Ito M, Matsuura T, Engel AG, Ohno K (2008) hnRNP H enhances skipping of a nonfunctional exon P3A in CHRNA1 and a mutation disrupting its binding causes congenital myasthenic syndrome. Hum Mol Genet 17:4022–4035. https://doi.org/10.1093/hmg/ddn305
doi: 10.1093/hmg/ddn305
pubmed: 18806275
pmcid: 2638575
Bian Y, Masuda A, Matsuura T, Ito M, Okushin K, Engel AG, Ohno K (2009) Tannic acid facilitates expression of the polypyrimidine tract binding protein and alleviates deleterious inclusion of CHRNA1 exon P3A due to an hnRNP H-disrupting mutation in congenital myasthenic syndrome. Hum Mol Genet 18:1229–1237. https://doi.org/10.1093/hmg/ddp023
doi: 10.1093/hmg/ddp023
pubmed: 19147685
pmcid: 2655771
Rahman MA, Masuda A, Ohe K, Ito M, Hutchinson DO, Mayeda A, Engel AG, Ohno K (2013) HnRNP L and hnRNP LL antagonistically modulate PTB-mediated splicing suppression of CHRNA1 pre-mRNA. Sci Rep 3. https://doi.org/10.1038/srep02931 .
DeChiara TM, Bowen DC, Valenzuela DM, Simmons MV, Poueymirou WT, Thomas S, Kinetz E, Compton DL et al (1996) The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo. Cell 85:501–512. https://doi.org/10.1016/S0092-8674(00)81251-9
doi: 10.1016/S0092-8674(00)81251-9
pubmed: 8653786
Kim N, Burden SJ (2008) MuSK controls where motor axons grow and form synapses. Nat Neurosci 11:19–27. https://doi.org/10.1038/nn2026
doi: 10.1038/nn2026
pubmed: 18084289
Zhou H, Glass DJ, Yancopoulos GD, Sanes JR (1999) Distinct domains of MuSK mediate its abilities to induce and to associate with postsynaptic specializations. J Cell Biol 146:1133–1146. https://doi.org/10.1083/jcb.146.5.1133
doi: 10.1083/jcb.146.5.1133
pubmed: 10477765
pmcid: 2169478
Roszmusz E, Patthy A, Trexler M, Patthy L (2001) Localization of disulfide bonds in the frizzled module of Ror1 receptor tyrosine kinase. J Biol Chem 276:18485–18490. https://doi.org/10.1074/jbc.M100100200
doi: 10.1074/jbc.M100100200
pubmed: 11279007
Gordon LR, Gribble KD, Syrett CM, Granato M (2012) Initiation of synapse formation by Wnt-induced MuSK endocytosis. Development. 139:1023–1033. https://doi.org/10.1242/dev.071555
doi: 10.1242/dev.071555
pubmed: 22318632
pmcid: 3274363
Nasrin F, Rahman MA, Masuda A, Ohe K, Takeda JI, Ohno K (2014) HnRNP C, YB-1 and hnRNP L coordinately enhance skipping of human musk exon 10 to generate a wnt-insensitive musk isoform. Sci Rep 4. https://doi.org/10.1038/srep06841 .
Kimbell LM, Ohno K, Engel AG, Rotundo RL (2004) C-terminal and heparin-binding domains of collagenic tail subunit are both essential for anchoring acetylcholinesterase at the synapse. J Biol Chem 279:10997–11005. https://doi.org/10.1074/jbc.M305462200
doi: 10.1074/jbc.M305462200
pubmed: 14702351
Ohno K, Ohkawara B, Ito M, Engel AG (2014) Molecular genetics of congenital myasthenic syndromes, in: ELS.
Rahman MA, Azuma Y, Nasrin F, Takeda JI, Nazim M, Bin Ahsan K, Masuda A, Engel AG, Ohno K (2015) SRSF<inf>1</inf> and hnRNP H antagonistically regulate splicing of COLQ exon 16 in a congenital myasthenic syndrome Sci Rep 5. https://doi.org/10.1038/srep13208 .
Leehey MA (2009) Fragile X-associated tremor/ataxia syndrome: clinical phenotype, diagnosis, and treatment. J Investig Med 57(8):830–836. https://doi.org/10.2310/JIM.0b013e3181af59c4
doi: 10.2310/JIM.0b013e3181af59c4
pubmed: 19574929
pmcid: 19574929
Sofola OA, Jin P, Qin Y, Duan R, Liu H, de Haro M, Nelson DL, Botas J (2007) RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG Premutation repeat-induced neurodegeneration in a drosophila model of FXTAS. Neuron. 55:565–571. https://doi.org/10.1016/j.neuron.2007.07.021
doi: 10.1016/j.neuron.2007.07.021
pubmed: 17698010
pmcid: 2215388
Iwahashi CK, Yasui DH, An HJ, Greco CM, Tassone F, Nannen K, Babineau B, Lebrilla CB et al (2006) Protein composition of the intranuclear inclusions of FXTAS. Brain. 129:256–271. https://doi.org/10.1093/brain/awh650
doi: 10.1093/brain/awh650
pubmed: 16246864
He F, Krans A, Freibaum BD, Paul Taylor J, Todd PK (2014) TDP-43 suppresses CGG repeat-induced neurotoxicity through interactions with HnRNP A2/B1. Hum Mol Genet 23:5036–5051. https://doi.org/10.1093/hmg/ddu216
doi: 10.1093/hmg/ddu216
pubmed: 24920338
pmcid: 4159148
Tan H, Poidevin M, Li H, Chen D, Jin P (2012) MicroRNA-277 modulates the neurodegeneration caused by fragile X premutation rCGG repeats. PLoS Genet 8. https://doi.org/10.1371/journal.pgen.1002681 .
Tan H, Qurashi A, Poidevin M, Nelson DL, Li H, Jin P (2012) Retrotransposon activation contributes to fragile X premutation rCGG-mediated neurodegeneration. Hum Mol Genet 21:57–65. https://doi.org/10.1093/hmg/ddr437
doi: 10.1093/hmg/ddr437
pubmed: 21940752
Sellier C, Rau F, Liu Y, Tassone F, Hukema RK, Gattoni R, Schneider A, Richard S et al (2010) Sam68 sequestration and partial loss of function are associated with splicing alterations in FXTAS patients. EMBO J 29:1248–1261. https://doi.org/10.1038/emboj.2010.21
doi: 10.1038/emboj.2010.21
pubmed: 20186122
pmcid: 2857464
Modrek B, Lee C (2002) A genomic view of alternative splicing. Nat Genet 30:13–19. https://doi.org/10.1038/ng0102-13
doi: 10.1038/ng0102-13
pubmed: 11753382
Lemmens R, Moore MJ, Al-Chalabi A, Brown RH, Robberecht W (2010) RNA metabolism and the pathogenesis of motor neuron diseases. Trends Neurosci 33:249–258. https://doi.org/10.1016/j.tins.2010.02.003
doi: 10.1016/j.tins.2010.02.003
pubmed: 20227117