Structural insights into how Prp5 proofreads the pre-mRNA branch site.

Actins / genetics Adenosine / metabolism Binding Sites Cryoelectron Microscopy DEAD-box RNA Helicases / chemistry Models, Molecular Mutation Protein Domains RNA Precursors / chemistry RNA Splicing / genetics Ribonucleoprotein, U1 Small Nuclear / metabolism Ribonucleoprotein, U2 Small Nuclear / chemistry Saccharomyces cerevisiae / enzymology Saccharomyces cerevisiae Proteins / chemistry Spliceosomes / chemistry

Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
08 2021
Historique:
received: 10 12 2020
accepted: 30 06 2021
pubmed: 6 8 2021
medline: 27 8 2021
entrez: 5 8 2021
Statut: ppublish

Résumé

During the splicing of introns from precursor messenger RNAs (pre-mRNAs), the U2 small nuclear ribonucleoprotein (snRNP) must undergo stable integration into the spliceosomal A complex-a poorly understood, multistep process that is facilitated by the DEAD-box helicase Prp5 (refs.

Identifiants

DOI: 10.1038/s41586-021-03789-5 PMID: 34349264 PMC: PMC8357632
pubmed: 34349264
doi: 10.1038/s41586-021-03789-5
pii: 10.1038/s41586-021-03789-5
pmc: PMC8357632
doi:

Substances chimiques

Actins 0
HSH155 protein, S cerevisiae 0
Prp40 protein, S cerevisiae 0
RNA Precursors 0
Ribonucleoprotein, U1 Small Nuclear 0
Ribonucleoprotein, U2 Small Nuclear 0
Saccharomyces cerevisiae Proteins 0
PRP5 protein, S cerevisiae EC 3.6.1.-
DEAD-box RNA Helicases EC 3.6.4.13
Adenosine K72T3FS567

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

296-300

Informations de copyright

© 2021. The Author(s).

Références

Ruby, S. W., Chang, T. H. & Abelson, J. Four yeast spliceosomal proteins (PRP5, PRP9, PRP11, and PRP21) interact to promote U2 snRNP binding to pre-mRNA. Genes Dev. 7, 1909–1925 (1993).
pubmed: 8405998 doi: 10.1101/gad.7.10.1909
Abu Dayyeh, B. K., Quan, T. K., Castro, M. & Ruby, S. W. Probing interactions between the U2 small nuclear ribonucleoprotein and the DEAD-box protein, Prp5. J. Biol. Chem. 277, 20221–20233 (2002).
pubmed: 11927574 doi: 10.1074/jbc.M109553200
Perriman, R., Barta, I., Voeltz, G. K., Abelson, J. & Ares, M. Jr. ATP requirement for Prp5p function is determined by Cus2p and the structure of U2 small nuclear RNA. Proc. Natl Acad. Sci. USA 100, 13857–13862 (2003).
pubmed: 14610285 pmcid: 283511 doi: 10.1073/pnas.2036312100
Xu, Y. Z. et al. Prp5 bridges U1 and U2 snRNPs and enables stable U2 snRNP association with intron RNA. EMBO J. 23, 376–385 (2004).
pubmed: 14713954 pmcid: 1271757 doi: 10.1038/sj.emboj.7600050
Xu, Y. Z. & Query, C. C. Competition between the ATPase Prp5 and branch region-U2 snRNA pairing modulates the fidelity of spliceosome assembly. Mol. Cell 28, 838–849 (2007).
pubmed: 18082608 pmcid: 2246091 doi: 10.1016/j.molcel.2007.09.022
Smith, D. J., Konarska, M. M. & Query, C. C. Insights into branch nucleophile positioning and activation from an orthogonal pre-mRNA splicing system in yeast. Mol. Cell 34, 333–343 (2009).
pubmed: 19450531 pmcid: 2730498 doi: 10.1016/j.molcel.2009.03.012
Rauhut, R. et al. Molecular architecture of the Saccharomyces cerevisiae activated spliceosome. Science 353, 1399–1405 (2016).
pubmed: 27562955 doi: 10.1126/science.aag1906
Yan, C., Wan, R., Bai, R., Huang, G. & Shi, Y. Structure of a yeast activated spliceosome at 3.5 Å resolution. Science 353, 904–911 (2016).
pubmed: 27445306 doi: 10.1126/science.aag0291
Haselbach, D. et al. Structure and conformational dynamics of the human spliceosomal B
pubmed: 29361316 doi: 10.1016/j.cell.2018.01.010
Zhang, X. et al. Structure of the human activated spliceosome in three conformational states. Cell Res. 28, 307–322 (2018).
pubmed: 29360106 pmcid: 5835773 doi: 10.1038/cr.2018.14
Zhang, Z. et al. Molecular architecture of the human 17S U2 snRNP. Nature 583, 310–313 (2020).
pubmed: 32494006 doi: 10.1038/s41586-020-2344-3
Plaschka, C., Lin, P. C. & Nagai, K. Structure of a pre-catalytic spliceosome. Nature 546, 617–621 (2017).
pubmed: 28530653 pmcid: 5503131 doi: 10.1038/nature22799
Bai, R., Wan, R., Yan, C., Lei, J. & Shi, Y. Structures of the fully assembled Saccharomyces cerevisiae spliceosome before activation. Science 360, 1423–1429 (2018).
pubmed: 29794219 doi: 10.1126/science.aau0325
Perriman, R. & Ares, M. Jr. Invariant U2 snRNA nucleotides form a stem loop to recognize the intron early in splicing. Mol. Cell 38, 416–427 (2010).
pubmed: 20471947 pmcid: 2872779 doi: 10.1016/j.molcel.2010.02.036
Plaschka, C., Lin, P. C., Charenton, C. & Nagai, K. Prespliceosome structure provides insights into spliceosome assembly and regulation. Nature 559, 419–422 (2018).
pubmed: 29995849 pmcid: 6141012 doi: 10.1038/s41586-018-0323-8
Liang, W. W. & Cheng, S. C. A novel mechanism for Prp5 function in prespliceosome formation and proofreading the branch site sequence. Genes Dev. 29, 81–93 (2015).
pubmed: 25561497 pmcid: 4281567 doi: 10.1101/gad.253708.114
Tang, Q. et al. SF3B1/Hsh155 HEAT motif mutations affect interaction with the spliceosomal ATPase Prp5, resulting in altered branch site selectivity in pre-mRNA splicing. Genes Dev. 30, 2710–2723 (2016).
pubmed: 28087715 pmcid: 5238730 doi: 10.1101/gad.291872.116
Li, X. et al. A unified mechanism for intron and exon definition and back-splicing. Nature 573, 375–380 (2019).
pubmed: 31485080 pmcid: 6939996 doi: 10.1038/s41586-019-1523-6
Carrocci, T. J., Paulson, J. C. & Hoskins, A. A. Functional analysis of Hsh155/SF3b1 interactions with the U2 snRNA/branch site duplex. RNA 24, 1028–1040 (2018).
pubmed: 29752352 pmcid: 6049509 doi: 10.1261/rna.065664.118
Kennedy, S. D., Bauer, W. J., Wang, W. & Kielkopf, C. L. Dynamic stacking of an expected branch point adenosine in duplexes containing pseudouridine-modified or unmodified U2 snRNA sites. Biochem. Biophys. Res. Commun. 511, 416–421 (2019).
pubmed: 30797552 pmcid: 6402984 doi: 10.1016/j.bbrc.2019.02.073
Shao, W., Kim, H. S., Cao, Y., Xu, Y. Z. & Query, C. C. A. A U1-U2 snRNP interaction network during intron definition. Mol. Cell. Biol. 32, 470–478 (2012).
pubmed: 22064476 pmcid: 3255776 doi: 10.1128/MCB.06234-11
Beier, D. H. et al. Dynamics of the DEAD-box ATPase Prp5 RecA-like domains provide a conformational switch during spliceosome assembly. Nucleic Acids Res. 47, 10842–10851 (2019).
pubmed: 31712821 pmcid: 6846040 doi: 10.1093/nar/gkz765
Yean, S. L. & Lin, R. J. U4 small nuclear RNA dissociates from a yeast spliceosome and does not participate in the subsequent splicing reaction. Mol. Cell. Biol. 11, 5571–5577 (1991).
pubmed: 1833635 pmcid: 361927
Bertram, K. et al. Cryo-EM structure of a human spliceosome activated for step 2 of splicing. Nature 542, 318–323 (2017).
pubmed: 28076346 doi: 10.1038/nature21079
Yang, B. et al. Identification of cross-linked peptides from complex samples. Nat. Methods 9, 904–906 (2012).
pubmed: 22772728 doi: 10.1038/nmeth.2099
Chen, Z. L. et al. A high-speed search engine pLink 2 with systematic evaluation for proteome-scale identification of cross-linked peptides. Nat. Commun. 10, 3404 (2019).
pubmed: 31363125 pmcid: 6667459 doi: 10.1038/s41467-019-11337-z
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
pubmed: 28250466 pmcid: 5494038 doi: 10.1038/nmeth.4193
Zhang, K. Gctf: real-time CTF determination and correction. J. Struct. Biol. 193, 1–12 (2016).
pubmed: 26592709 pmcid: 4711343 doi: 10.1016/j.jsb.2015.11.003
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
pubmed: 28165473 doi: 10.1038/nmeth.4169
Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
doi: 10.1002/jcc.20084 pubmed: 15264254
Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126–2132 (2004).
pubmed: 15572765 doi: 10.1107/S0907444904019158
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010).
pubmed: 20124702 pmcid: 2815670 doi: 10.1107/S0907444909052925
Guex, N. & Peitsch, M. C. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18, 2714–2723 (1997).
pubmed: 9504803 doi: 10.1002/elps.1150181505
Kastner, B., Will, C. L., Stark, H. & Lührmann, R. Structural insights into nuclear pre-mRNA splicing in higher eukaryotes. Cold Spring Harb. Perspect. Biol. 11, a032417 (2019).
pubmed: 30765414 doi: 10.1101/cshperspect.a032417 pmcid: 6824238
Wilkinson, M. E., Charenton, C. & Nagai, K. RNA splicing by the spliceosome. Annu. Rev. Biochem. 89, 359–388 (2020).
pubmed: 31794245 doi: 10.1146/annurev-biochem-091719-064225
Semlow, D. R. & Staley, J. P. Staying on message: ensuring fidelity in pre-mRNA splicing. Trends Biochem. Sci. 37, 263–273 (2012).
pubmed: 22564363 pmcid: 3735133 doi: 10.1016/j.tibs.2012.04.001
Cordin, O. & Beggs, J. D. RNA helicases in splicing. RNA Biol. 10, 83–95 (2013).
pubmed: 23229095 pmcid: 3590240 doi: 10.4161/rna.22547
Kistler, A. L. & Guthrie, C. Deletion of MUD2, the yeast homolog of U2AF65, can bypass the requirement for sub2, an essential spliceosomal ATPase. Genes Dev. 15, 42–49 (2001).
pubmed: 11156604 pmcid: 312603 doi: 10.1101/gad.851601
Zhang, M. & Green, M. R. Identification and characterization of yUAP/Sub2p, a yeast homolog of the essential human pre-mRNA splicing factor hUAP56. Genes Dev. 15, 30–35 (2001).
pubmed: 11156602 pmcid: 312605 doi: 10.1101/gad.851701
O’Day, C. L., Dalbadie-McFarland, G. & Abelson, J. The Saccharomyces cerevisiae Prp5 protein has RNA-dependent ATPase activity with specificity for U2 small nuclear RNA. J. Biol. Chem. 271, 33261–33267 (1996).
pubmed: 8969184 doi: 10.1074/jbc.271.52.33261
Wang, Q., Zhang, L., Lynn, B. & Rymond, B. C. A. A BBP-Mud2p heterodimer mediates branchpoint recognition and influences splicing substrate abundance in budding yeast. Nucleic Acids Res. 36, 2787–2798 (2008).
pubmed: 18375978 pmcid: 2377449 doi: 10.1093/nar/gkn144
Jacewicz, A., Chico, L., Smith, P., Schwer, B. & Shuman, S. Structural basis for recognition of intron branchpoint RNA by yeast Msl5 and selective effects of interfacial mutations on splicing of yeast pre-mRNAs. RNA 21, 401–414 (2015).
pubmed: 25587180 pmcid: 4338336 doi: 10.1261/rna.048942.114
Cretu, C. et al. Structural basis of splicing modulation by antitumor macrolide compounds. Mol. Cell 70, 265–273.e8 (2018).
pubmed: 29656923 doi: 10.1016/j.molcel.2018.03.011
Lin, P. C. & Xu, R. M. Structure and assembly of the SF3a splicing factor complex of U2 snRNP. EMBO J. 31, 1579–1590 (2012).
pubmed: 22314233 pmcid: 3321192 doi: 10.1038/emboj.2012.7
Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D 74, 531–544 (2018).
doi: 10.1107/S2059798318006551
Ester, C. & Uetz, P. The FF domains of yeast U1 snRNP protein Prp40 mediate interactions with Luc7 and Snu71. BMC Biochem. 9, 29 (2008).
pubmed: 19014439 pmcid: 2613882 doi: 10.1186/1471-2091-9-29
Caspary, F. & Séraphin, B. The yeast U2A′/U2B complex is required for pre-spliceosome formation. EMBO J. 17, 6348–6358 (1998).
pubmed: 9799242 pmcid: 1170959 doi: 10.1093/emboj/17.21.6348

Auteurs

Zhenwei Zhang (Z)

Department of Structural Dynamics, MPI for Biophysical Chemistry, Göttingen, Germany.
ORCID: 0000-0003-2906-9346

Norbert Rigo (N)

Cellular Biochemistry, MPI for Biophysical Chemistry, Göttingen, Germany.

Olexandr Dybkov (O)

Cellular Biochemistry, MPI for Biophysical Chemistry, Göttingen, Germany.

Jean-Baptiste Fourmann (JB)

Cellular Biochemistry, MPI for Biophysical Chemistry, Göttingen, Germany.

Cindy L Will (CL)

Cellular Biochemistry, MPI for Biophysical Chemistry, Göttingen, Germany.

Vinay Kumar (V)

Cellular Biochemistry, MPI for Biophysical Chemistry, Göttingen, Germany.
ORCID: 0000-0001-6642-8876

Henning Urlaub (H)

Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Göttingen, Germany.
Bioanalytics Group, Institute for Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
ORCID: 0000-0003-1837-5233

Holger Stark (H)

Department of Structural Dynamics, MPI for Biophysical Chemistry, Göttingen, Germany. hstark1@gwdg.de.
ORCID: 0000-0002-6161-1118

Reinhard Lührmann (R)

Cellular Biochemistry, MPI for Biophysical Chemistry, Göttingen, Germany. reinhard.luehrmann@mpibpc.mpg.de.
ORCID: 0000-0003-3253-7518

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines des microfilaments › Actines › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléosides › Ribonucléosides › Adénosine › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Techniques d'investigation › Microscopie électronique › Cryomicroscopie électronique › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Nucleotidyltransferases › RNA nucleotidyltransferases › RNA helicases › DEAD-box RNA helicases › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Structure tertiaire des protéines › Domaines protéiques › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › Précurseurs des ARN › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Maturation post-transcriptionnelle des ARN › Épissage des ARN › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Facteurs d'épissage des ARN › Petites ribonucléoprotéines nucléaires U1 › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Facteurs d'épissage des ARN › Petites ribonucléoprotéines nucléaires U2 › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Eucaryotes › Champignons › Levures › Saccharomyces › Saccharomyces cerevisiae › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines fongiques › Protéines de Saccharomyces cerevisiae › Structural insights into how Prp5 proofreads...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Structures nucléaires › Espace intranucléaire › Splicéosomes › Structural insights into how Prp5 proofreads...