Emerging roles of alternative cleavage and polyadenylation (APA) in human disease.
3'-UTR
RNA binding proteins
RNA biology
alternative cleavage and polyadenylation
mRNA maturation
polyadenylation
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
13
07
2021
received:
05
06
2021
accepted:
20
07
2021
pubmed:
12
8
2021
medline:
6
5
2022
entrez:
11
8
2021
Statut:
ppublish
Résumé
In the messenger RNA (mRNA) maturation process, the 3'-end of pre-mRNA is cleaved and a poly(A) sequence is added, this is an important determinant of mRNA stability and its cellular functions. More than 60%-70% of human genes have three or more polyadenylation (APA) sites and can be cleaved at different sites, generating mRNA transcripts of varying lengths. This phenomenon is termed as alternative cleavage and polyadenylation (APA) and it plays role in key biological processes like gene regulation, cell proliferation, senescence, and also in various human diseases. Loss of regulatory microRNA binding sites and interactions with RNA-binding proteins leading to APA are largely investigated in human diseases. However, the functions of the core APA machinery and related factors during disease conditions remain largely unknown. In this review, we discuss the roles of polyadenylation machinery in relation to brain disease, cardiac failure, pulmonary fibrosis, cancer, infectious conditions, and other human diseases. Collectively, we believe this review will be a useful avenue for understanding the emerging role of APA in the pathobiology of various human diseases.
Substances chimiques
3' Untranslated Regions
0
RNA, Messenger
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
149-160Subventions
Organisme : CSR NIH HHS
ID : 5R01HL138510
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 19TPA34880039 and 18IPA34170497
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Afonso-Grunz, F. (2015). Putative alternative polyadenylation (APA) events in the early interaction of Salmonella enterica Typhimurium and human host cells, Genomics Data, 6, 222-227. https://doi.org/10.1016/j.gdata.2015.10.001
Alcott, C. E., Yalamanchili, H. K., Ji, P., van der Heijden, M. E., Saltzman, A., Elrod, N., Lin, A., Leng, M., Bhatt, B., Hao, S., Wang, Q., Saliba, A., Tang, J., Malovannaya, A., Wagner, E. J., Liu, Z., & Zoghbi, H. Y. (2020). Partial loss of CFIM25 causes learning deficits and aberrant neuronal alternative polyadenylation. eLife, 9, 9. https://doi.org/10.7554/eLife.50895
Arefeen, A., Liu, J., Xiao, X., & Jiang, T. (2018). TAPAS: Tool for alternative polyadenylation site analysis. Bioinformatics, 34(15), 2521-2529. https://doi.org/10.1093/bioinformatics/bty110
Batra, R., Charizanis, K., Manchanda, M., Mohan, A., Li, M., Finn, D. J., Goodwin, M., Zhang, C., Sobczak, K., Thornton, C. A., & Swanson, M. S. (2014). Loss of MBNL leads to disruption of developmentally regulated alternative polyadenylation in RNA-mediated disease. Molecular Cell, 56(2), 311-322. https://doi.org/10.1016/j.molcel.2014.08.027
Bava, F. A., Eliscovich, C., Ferreira, P. G., Miñana, B., Ben-Dov, C., Guigó, R., Valcácel, J., & Méndez, R. (2013). CPEB1 coordinates alternative 3′-UTR formation with translational regulation. Nature, 495(7439), 121-125. https://doi.org/10.1038/nature11901
Berkovits, B. D., & Mayr, C. (2015). Alternative 3′ UTRs act as scaffolds to regulate membrane protein localization. Nature, 522(7556), 363-367. https://doi.org/10.1038/nature14321
Brumbaugh, J., Di Stefano, B., Wang, X., Borkent, M., Forouzmand, E., Clowers, K. J., Ji, F., Schwarz, B. A., Kalocsay, M., Elledge, S. J., Chen, Y., Sadreyev, R. I., Gygi, S. P., Hu, G., Shi, Y., & Hochedlinger, K. (2018). Nudt21 controls cell fate by connecting alternative polyadenylation to chromatin signaling. Cell, 172(1-2), 106-120. https://doi.org/10.1016/j.cell.2017.11.023
Cao, J., Belanger, K., Jaworski, E., Rayavara, K., Nutter, C., Ji, P., Elrod, N., Verma, S., Widen, S., Wagner, E. J., Garg, N., Routh, A. L., & Kuyumcu-Martinez, M. (2019). Abstract 321: RBFOX2 is critical for maintaining alternative polyadenylation patterns in cardiomyoblasts. Circulation Research, 125(suppl_1), https://doi.org/10.1161/res.125.suppl_1.321
Chang, H., Lim, J., Ha, M., & Kim, V. N. (2014). TAIL-seq: Genome-wide determination of poly(A) tail length and 3' end modifications. Molecular Cell, 53(6), 1044-1052. https://doi.org/10.1016/j.molcel.2014.02.007
Chang, J.-W., Yeh, H.-S., & Yong, J. (2017). Alternative polyadenylation in human diseases. Endocrinology and Metabolism, 32(4), 413-421. https://doi.org/10.3803/ENM.2017.32.4.413
Chen, X., Zhang, J. X., Luo, J. H., Wu, S., Yuan, G. J., Ma, N. F., Feng, Y., Cai, M. Y., Chen, R. X., Lu, J., Jiang, L. J., Chen, J. W., Jin, X. H., Liu, H. L., Chen, W., Guan, X. Y., Kang, T. B., Zhou, F. J., & Xie, D. (2018). CSTF2-induced shortening of the RAC1 3′UTR promotes the pathogenesis of urothelial carcinoma of the bladder. Cancer Research, 78(20), 5848-5862. https://doi.org/10.1158/0008-5472.CAN-18-0822
Chen, S. L., Zhu, Z. X., Yang, X., Liu, L. L., He, Y. F., Yang, M. M., Guan, X. Y., Wang, X., & Yun, J. P. (2021). Cleavage and polyadenylation specific factor 1 promotes tumor progression via alternative polyadenylation and splicing in hepatocellular carcinoma. Frontiers in Cell and Developmental Biology, 9, 616835. https://doi.org/10.3389/FCELL.2021.616835
Chorghade, S., Seimetz, J., Emmons, R., Yang, J., Bresson, S. M., de Lisio, M., Parise, G., Conrad, N. K., & Kalsotra, A. (2017). Poly(A) tail length regulates PABPC1 expression to tune translation in the heart. eLife, 6, 1-19. https://doi.org/10.7554/eLife.24139
Chuvpilo, S, Zimmer, M., Kerstan, A., Glöckner, J., Avots, A., Escher, C., Fischer, C., Inashkina, I., Jankevics, E., Berberich-Siebelt, F., Schmitt, E., & Serfling, E. (1999). Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells. Immunity, 10(2), 261-269. https://doi.org/10.1016/S1074-7613(00)80026-6
Creemers, E. E., Bawazeer, A., Van Ugalde, A. P., Van Deutekom, H. W. M., Der Made, I., De Groot, N. E., Adriaens, M. E., Cook, S. A., Van Bezzina, C. R., Hubner, N., Der Velden, J., Elkon, R., Agami, R., & Pinto, Y. M. (2016). Genome-wide polyadenylation maps reveal dynamic mRNA 3′-end formation in the failing human heart. Circulation Research, 118(3), 433-438. https://doi.org/10.1161/CIRCRESAHA.115.307082
Curinha, A., Braz, S. O., Pereira-Castro, I., Cruz, A., & Moreira, A. (2014). Implications of polyadenylation in health and disease. Nucleus, 5(6), 508-519. https://doi.org/10.4161/NUCL.36360
Derti, A., Garrett-Engele, P., MacIsaac, K. D., Stevens, R. C., Sriram, S., Chen, R., Rohl, C. A., Johnson, J. M., & Babak, T. (2012). A quantitative atlas of polyadenylation in five mammals. Genome Research, 22(6), 1173-1183. https://doi.org/10.1101/gr.132563.111
De Vooght, K. M. K., Wijk, R., Van, & Van Solinge, W. W. (2009). Management of gene promoter mutations in molecular diagnostics. Clinical Chemistry, 55(4), 698-708. https://doi.org/10.1373/clinchem.2008.120931
Elkon, R., Ugalde, A. P., & Agami, R. (2013). Alternative cleavage and polyadenylation: Extent, regulation and function. Nature Reviews Genetics, 14(7), 496-506. https://doi.org/10.1038/nrg3482
Erson-Bensan, A. E. (2016). Alternative polyadenylation and RNA-binding proteins. Journal of Molecular Endocrinology, 57(2), F29-F34. https://doi.org/10.1530/JME-16-0070
Fahmi, N. A., Chang, J.-W., Nassereddeen, H., Ahmed, K. T., Fan, D., Yong, J., & Zhang, W. (2020). APA-Scan: Detection and visualization of 3'-UTR APA with RNA-seq and 3'-end-seq data. BioRxiv, 2020, 951657. https://doi.org/10.1101/2020.02.16.951657
Fischl, H., Neve, J., Wang, Z., Patel, R., Louey, A., Tian, B., & Furger, A. (2019). hnRNPC regulates cancer-specific alternative cleavage and polyadenylation profiles. Nucleic Acids Research, 47(14), 7580-7591. https://doi.org/10.1093/nar/gkz461
Gao, Y., Li, L., Amos, C. I., & Li, W. (2021). Analysis of alternative polyadenylation from single-cell RNA-seq using scDaPars reveals cell subpopulations invisible to gene expression. Genome Research, https://doi.org/10.1101/gr.271346.120
Garin, I., Edghill, E. L., Akerman, I., Rubio-Cabezas, O., Rica, I., Locke, J. M., Maestro, M. A., Alshaikh, A., Bundak, R., Castillo, G., del Deeb, A., Deiss, D., Fernandez, J. M., Godbole, K., Hussain, K., O′Connell, M., Klupa, T., Kolouskova, S., Mohsin, F., & Hattersley, A. T. (2010). Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis. Proceedings of the National Academy of Sciences of the United States of America, 107(7), 3105-3110. https://doi.org/10.1073/PNAS.0910533107
Gillen, A. E., Brechbuhl, H. M., Yamamoto, T. M., Kline, E., Pillai, M. M., Berth, J. R. H., & Kabos, P. (2017). Alternative polyadenylation of PRELID1 regulates mitochondrial ROS signaling and cancer outcomes. Molecular Cancer Research, 15(12), 1741-1751. https://doi.org/10.1158/1541-7786.MCR-17-0010
Grassi, E., Santoro, R., Umbach, A., Grosso, A., Oliviero, S., Neri, F., Conti, L., Ala, U., Provero, P., Dicunto, F., & Merlo, G. R. (2019). Choice of alternative polyadenylation sites, mediated by the RNA-binding protein Elavl3, plays a role in differentiation of inhibitory neuronal progenitors. Frontiers in Cellular Neuroscience, 12, 12. https://doi.org/10.3389/fncel.2018.00518
Grozdanov, P. N., Masoumzadeh, E., Latham, M. P., & MacDonald, C. C. (2018). The structural basis of CstF-77 modulation of cleavage and polyadenylation through stimulation of CstF-64 activity. Nucleic Acids Research, 46(22), 12022-12039. https://doi.org/10.1093/nar/gky862
Gruber, A. R., Martin, G., Keller, W., & Zavolan, M. (2014). Means to an end: Mechanisms of alternative polyadenylation of messenger RNA precursors. Wiley Interdisciplinary Reviews: RNA, 5(2), 183-196. https://doi.org/10.1002/wrna.1206
Guvenek, A., & Tian, B. (2018). Analysis of alternative cleavage and polyadenylation in mature and differentiating neurons using RNA-seq data. Quantitative Biology, 6(3), 253-266. https://doi.org/10.1007/s40484-018-0148-3
Göpferich, M., Oommen George, N., Domingo Muelas, A., Bizyn, A., Pascual, R., Fijalkowska, D., Kalamakis, G., Müller, U., Krijgsveld, J., Mendez, R., Fariñas, I., Huber, W., Anders, S., & Martin-Villalba, A. (2020). Single cell 3'UTR analysis identifies changes in alternative polyadenylation throughout neuronal differentiation and in autism. BioRxiv, https://doi.org/10.1101/2020.08.12.247627
Ha, K. C. H., Blencowe, B. J., & Morris, Q. (2018). QAPA: A new method for the systematic analysis of alternative polyadenylation from RNA-seq data. Genome Biology, 19(1), 1-18. https://doi.org/10.1186/s13059-018-1414-4
Harteveld, C. L., Losekoot, M., Haak, H., Heister, G. A., Giordano, P. C., & Bernini, L. F. (1994). A novel polyadenylation signal mutation in the alpha 2-globin gene causing alpha thalassaemia. British Journal of Haematology, 87(1), 139-143. https://doi.org/10.1111/J.1365-2141.1994.TB04883.X
Haabeth, O. A. W., Blake, T. R., McKinlay, C. J., Waymouth, R. M., Wender, P. A., & Levy, R. (2018). mRNA vaccination with charge-altering releasable transporters elicits human T cell responses and cures established tumors in mice. Proceedings of the National Academy of Sciences of the United States of America, 115(39), E9153-E9161. https://doi.org/10.1073/pnas.1810002115
Hall-Pogar, T., Liang, S., Hague, L. K., & Lutz, C. S. (2007). Specific trans-acting proteins interact with auxiliary RNA polyadenylation elements in the COX-2 3′-UTR. RNA, 13(7), 1103-1115. https://doi.org/10.1261/rna.577707
Hartley, C. A., McKenna, M. C., Salman, R., Holmes, A., Casey, B. J., Phelps, E. A., & Glatt, C. E. (2012). Serotonin transporter polyadenylation polymorphism modulates the retention of fear extinction memory. Proceedings of the National Academy of Sciences of the United States of America, 109(14), 5493-5498. https://doi.org/10.1073/PNAS.1202044109
Hong, W., Ruan, H., Zhang, Z., Ye, Y., Liu, Y., Li, S., Jing, Y., Zhang, H., Diao, L., Liang, H., & Han, L. (2020). APAatlas: Decoding alternative polyadenylation across human tissues. Nucleic Acids Research, 48(D1), D34-D39. https://doi.org/10.1093/NAR/GKZ876
Huang, J., Weng, T., Ko, J., Chen, N. Y., Xiang, Y., Volcik, K., Han, L., Blackburn, M. R., & Lu, X. (2018). Suppression of cleavage factor Im 25 promotes the proliferation of lung cancer cells through alternative polyadenylation. Biochemical and Biophysical Research Communications, 503(2), 856-862. https://doi.org/10.1016/j.bbrc.2018.06.087
Jackson, N. A. C., Kester, K. E., Casimiro, D., Gurunathan, S., & DeRosa, F. (2020). The promise of mRNA vaccines: A biotech and industrial perspective. NPJ Vaccines, 5(1), 1-6. https://doi.org/10.1038/s41541-020-0159-8
Jalkanen, A. L., Coleman, S. J., & Wilusz, J. (2014). Determinants and implications of mRNA poly(A) tail size-Does this protein make my tail look big? Seminars in Cell and Developmental Biology, 34, 24-32. https://doi.org/10.1016/j.semcdb.2014.05.018
Jenal, M., Elkon, R., Loayza-Puch, F., Van Haaften, G., Kühn, U., Menzies, F. M., Vrielink, J. A. F. O., Bos, A. J., Drost, J., Rooijers, K., Rubinsztein, D. C., & Agami, R. (2012). The poly(A)-binding protein nuclear 1 suppresses alternative cleavage and polyadenylation sites. Cell, 149(3), 538-553. https://doi.org/10.1016/j.cell.2012.03.022
Jensen, M. K., Elrod, N. D., Yalamanchili, H. K., Ji, P., Lin, A., Liu, Z., & Wagner, E. J. (2021). Application and design considerations for 3'-end sequencing using click-chemistry. Methods in Enzymology, 655, 1-23. https://doi.org/10.1016/BS.MIE.2021.03.012
Ji, Z., & Tian, B. (2009). Reprogramming of 3′ untranslated regions of mRNAs by alternative polyadenylation in generation of pluripotent stem cells from different cell types. PLOS One, 4(12), e8419. https://doi.org/10.1371/journal.pone.0008419
Jia, X., Yuan, S., Wang, Y., Fu, Y., Ge, Y., Ge, Y., Lan, X., Feng, Y., Qiu, F., Li, P., Chen, S., & Xu, A. (2017). The role of alternative polyadenylation in the antiviral innate immune response. Nature Communications, 8, 14605. https://doi.org/10.1038/ncomms14605
Katz, Y., Wang, E. T., Airoldi, E. M., & Burge, C. B. (2010). Analysis and design of RNA sequencing experiments for identifying isoform regulation. Nature Methods, 7(12), 1009-1015. https://doi.org/10.1038/nmeth.1528
Kini, H. K., Silverman, I. M., Ji, X., Gregory, B. D., & Liebhaber, S. A. (2016). Cytoplasmic poly(A) binding protein-1 binds to genomically encoded sequences within mammalian mRNAs. RNA, 22(1), 61-74. https://doi.org/10.1261/rna.053447.115
Ko, J., Mills, T., Huang, J., Chen, N. Y., Mertens, T. C. J., Collum, S. D., Lee, G., Xiang, Y., Han, L., Zhou, Y., Lee, C. G., Elias, J. A., Jyothula, S. S. K., Rajagopal, K., Karmouty-Quintana, H., & Blackburn, M. R. (2019). Transforming growth factor β1 alters the 3'-UTR of mRNA to promote lung fibrosis. Journal of Biological Chemistry, 294(43), 15781-15794. https://doi.org/10.1074/jbc.RA119.009148
Kühn, U., Buschmann, J., & Wahle, E. (2017). The nuclear poly(A) binding protein of mammals, but not of fission yeast, participates in mRNA polyadenylation. RNA, 23(4), 473-482. https://doi.org/10.1261/rna.057026.116
Lan, Y. L., & Zhang, J. (2021). Modulation of untranslated region alternative polyadenylation in glioma tumorigenesis. Biomedicine & Pharmacotherapy, 137, 111416. https://doi.org/10.1016/J.BIOPHA.2021.111416
Le Pera, L., Mazzapioda, M., & Tramontano, A. (2015). 3USS: A web server for detecting alternative 3′-UTRs from RNA-seq experiments. Bioinformatics, 31(11), 1845-1847. https://doi.org/10.1093/bioinformatics/btv035
Licatalosi, D. D., Mele, A., Fak, J. J., Ule, J., Kayikci, M., Chi, S. W., Clark, T. A., Schweitzer, A. C., Blume, J. E., Wang, X., Darnell, J. C., & Darnell, R. B. (2008). HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature, 456(7221), 464-469. https://doi.org/10.1038/nature07488
Locke, J. M., Da, G., Xavier, S., Rutter, G. A., & Harries, L. W. (2011). An alternative polyadenylation signal in TCF7L2 generates isoforms that inhibit T cell factor/lymphoid-enhancer factor (TCF/LEF)-dependent target genes. Diabetologia, 54(12), 3078-302. https://doi.org/10.1007/s00125-011-2290-6
Lu, J., & Bushel, P. R. (2013). Dynamic expression of 3' UTRs revealed by Poisson hidden Markov modeling of RNA-Seq: Implications in gene expression profiling. Gene, 527(2), 616-623. https://doi.org/10.1016/j.gene.2013.06.052
Mao, Z., Zhao, H., Qin, Y., Wei, J., Sun, J., Zhang, W., & Kang, Y. (2020). Post-transcriptional dysregulation of microRNA and alternative polyadenylation in colorectal cancer. Frontiers in Genetics, 11, 1. https://doi.org/10.3389/fgene.2020.00064
Masamha, C. P., Xia, Z., Yang, J., Albrecht, T. R., Li, M., Shyu, A. B., Li, W., & Wagner, E. J. (2014). CFIm25 links alternative polyadenylation to glioblastoma tumour suppression. Nature, 510(7505), 412-416. https://doi.org/10.1038/nature13261
Masuda, A., Takeda, J. I., Okuno, T., Okamoto, T., Ohkawara, B., Ito, M., Ishigaki, S., Sobue, G., & Ohno, K. (2015). Position-specific binding of FUS to nascent RNA regulates mRNA length. Genes and Development, 29(10), 1045-1057. https://doi.org/10.1101/gad.255737.114
Mayo, E., & Park, M.A. (2021). The role of cytosolic polyadenylation element binding protein 2 alternative splicing in hypoxia. BioRxiv, 35(S1), https://doi.org/10.1101/2020.10.05.325290
Melamed, Z., López-Erauskin, J., Baughn, M. W., Zhang, O., Drenner, K., Sun, Y., Freyermuth, F., McMahon, M. A., Beccari, M. S., Artates, J. W., Ohkubo, T., Rodriguez, M., Lin, N., Wu, D., Bennett, C. F., Rigo, F., Da Cruz, S., Ravits, J., Lagier-Tourenne, C., & Cleveland, D. W. (2019). Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration. Nature Neuroscience, 22(2), 180-190. https://doi.org/10.1038/s41593-018-0293-z
Miura, P., Shenker, S., Andreu-Agullo, C., Westholm, J. O., & Lai, E. C. (2013). Widespread and extensive lengthening of 39 UTRs in the mammalian brain. Genome Research, 23(5), 812-825. https://doi.org/10.1101/gr.146886.112
Mohan, N., Kumar, V., Kandala, D. T., Kartha, C. C., & Laishram, R. S. (2018). A splicing-independent function of RBM10 controls specific 3′ UTR processing to regulate cardiac hypertrophy. Cell Reports, 24(13), 3539-3553. https://doi.org/10.1016/j.celrep.2018.08.077
Murphy, M. R., & Kleiman, F. E. (2020). Connections between 3′ end processing and DNA damage response: Ten years later. Wiley Interdisciplinary Reviews: RNA, 11(2) https://doi.org/10.1002/wrna.1571
Neve, J., Patel, R., Wang, Z., Louey, A., & Furger, A. M. (2017). Cleavage and polyadenylation: Ending the message expands gene regulation. RNA Biology, 14, 865-890. 7. https://doi.org/10.1080/15476286.2017.1306171
Nimura, K., Yamamoto, M., Takeichi, M., Saga, K., Takaoka, K., Kawamura, N., Nitta, H., Nagano, H., Ishino, S., Tanaka, T., Schwartz, R. J., Aburatani, H., & Kaneda, Y. (2016). Regulation of alternative polyadenylation by Nkx2-5 and Xrn2 during mouse heart development. ELife, 5, 5, https://doi.org/10.7554/elife.16030
Nourse, J., Spada, S., & Danckwardt, S. (2020). Emerging roles of RNA 3′-end cleavage and polyadenylation in pathogenesis, diagnosis and therapy of human disorders. Biomolecules, 10(6), 1-43. https://doi.org/10.3390/biom10060915
Olajuyin, A. M., Zhang, X., & Ji, H. L. (2019). Alveolar type 2 progenitor cells for lung injury repair. Cell Death Discovery, 5(1), 1234567890. https://doi.org/10.1038/s41420-019-0147-9
Pai, A. A., Baharian, G., Pagé Sabourin, A., Brinkworth, J. F., Nédélec, Y., Foley, J. W., Grenier, J. C., Siddle, K. J., Dumaine, A., Yotova, V., Johnson, Z. P., Lanford, R. E., Burge, C. B., & Barreiro, L. B. (2016). Widespread shortening of 3' untranslated regions and increased exon inclusion are evolutionarily conserved features of innate immune responses to infection. PLOS Genetics, 12(9), 1006338. https://doi.org/10.1371/journal.pgen.1006338
Park, J. Y., Li, W., Zheng, D., Zhai, P., Zhao, Y., Matsuda, T., Vatner, S. F., Sadoshima, J., & Tian, B. (2011). Comparative analysis of mRNA isoform expression in Cardiac hypertrophy and development reveals multiple Post-Transcriptional regulatory modules. PLOS One, 6(7), e22391. https://doi.org/10.1371/journal.pone.0022391
Patel, R., Brophy, C., Hickling, M., Neve, J., & Furger, A. (2019). Alternative cleavage and polyadenylation of genes associated with protein turnover and mitochondrial function are deregulated in Parkinson's, Alzheimer's and ALS disease. BMC Medical Genomics, 12(1), 60. https://doi.org/10.1186/s12920-019-0509-4
Rehfeld, A., Plass, M., Krogh, A., & Friis-Hansen, L. (2013). Alterations in polyadenylation and its implications for endocrine disease. Frontiers in Endocrinology, 4, 53. https://doi.org/10.3389/fendo.2013.00053
Rhinn, H., Qiang, L., Yamashita, T., Rhee, D., Zolin, A., Vanti, W., & Abeliovich, A. (2012). α-Synuclein transcript alternative 3′UTR usage as a convergent mechanism in Parkinson's disease pathology. Nature Communications, 3, 1084. https://doi.org/10.1038/NCOMMS2032
Romo, L., Ashar-Patel, A., Pfister, E., & Aronin, N. (2017). Alterations in mRNA 3′ UTR isoform abundance accompany gene expression changes in human Huntington's disease brains. Cell Reports, 20(13), 3057-3070. https://doi.org/10.1016/J.CELREP.2017.09.009
Romo, L., Mohn, E. S., & Aronin, N. (2018). A fresh look at Huntingtin mRNA processing in Huntington's disease. Journal of Huntington's Disease, 7(2), 101-108. https://doi.org/10.3233/JHD-180292
Sandberg, R., Neilson, J. R., Sarma, A., Sharp, P. A., & Burge, C. B. (2008). Proliferating cells express mRNAs with shortened 3′ untranslated regions and fewer microRNA target sites. Science, 320(5883), 1643-1647. https://doi.org/10.1126/science.1155390
Schäfer, P., Tüting, C., Schönemann, L., Kühn, U., Treiber, T., Treiber, N., Ihling, C., Graber, A., Keller, W., Meister, G., Sinz, A., & Wahle, E. (2018). Reconstitution of mammalian cleavage factor II involved in 3′ processing of mRNA precursors. RNA, 24(12), 1721-1737. https://doi.org/10.1261/rna.068056.118
Shan, L., Wu, C., Chen, D., Hou, L., Li, X., Wang, L., Chu, X., Hou, Y., & Wang, Z. (2017). Regulators of alternative polyadenylation operate at the transition from mitosis to meiosis. Journal of Genetics and Genomics, 44(2), 95-106. https://doi.org/10.1016/j.jgg.2016.12.007
Shi, Y., Di Giammartino, D. C., Taylor, D., Sarkeshik, A., Rice, W. J., Yates, J. R., Frank, J., & Manley, J. L. (2009). Molecular architecture of the human pre-mRNA 3′ processing complex. Molecular Cell, 33(3), 365-376. https://doi.org/10.1016/j.molcel.2008.12.028
Shu, L., Matveyenko, A. V., Kerr-Conte, J., Cho, J. H., McIntosh, C. H. S., & Maedler, K. (2009). Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function. Human Molecular Genetics, 18(13), 2388-2399. https://doi.org/10.1093/hmg/ddp178
Shulman, E. D., & Elkon, R. (2019). Cell-type-specific analysis of alternative polyadenylation using single-cell transcriptomics data. Nucleic Acids Research, 47(19), 10027-10039. https://doi.org/10.1093/nar/gkz781
Shulman, E. D., & Elkon, R. (2020). Systematic identification of functional SNPs interrupting 3'UTR polyadenylation signals. PLOS Genetics, 16(8), e1008977. https://doi.org/10.1371/JOURNAL.PGEN.1008977
Singh, I., Lee, S. H., Sperling, A. S., Samur, M. K., Tai, Y. T., Fulciniti, M., Munshi, N. C., Mayr, C., & Leslie, C. S. (2018). Widespread intronic polyadenylation diversifies immune cell transcriptomes. Nature Communications, 9(1), 1716. https://doi.org/10.1038/S41467-018-04112-Z
Sommerkamp, P., Cabezas-Wallscheid, N., & Trumpp, A. (2021). Alternative polyadenylation in stem cell self-renewal and differentiation. Trends in Molecular Medicine, 27(7), 660-672. https://doi.org/10.1016/J.MOLMED.2021.04.006
Spraggon, L., & Cartegni, L. (2013). U1 snrnp-dependent suppression of polyadenylation: Physiological role and therapeutic opportunities in cancer. International Journal of Cell Biology, 2013, 846510. https://doi.org/10.1155/2013/846510
Subramanian, A., Hall, M., Hou, H., Mufteev, M., Yu, B., Yuki, K., Nishimura, H., Sathaseevan, A., Lant, B., Zhai, B., Ellis, J., Wilson, M., Daugaard, M., & Derry, W. B. (2020). Alternative polyadenylation is a determinant of oncogenic Ras function. BioRxiv, https://doi.org/10.1101/2020.06.08.140145
Sudheesh, A. P., Mohan, N., Francis, N., Laishram, R. S., & Anderson, R. A. (2019). Star-PAP controlled alternative polyadenylation coupled poly(A) tail length regulates protein expression in hypertrophic heart. Nucleic Acids Research, 47(20), 10771-10787. https://doi.org/10.1093/nar/gkz875
Tamaddon, M., Shokri, G., Rad, S. M. A. H., Rad, I., Razavi, À. E., & Kouhkan, F. (2020). Involved microRNAs in alternative polyadenylation intervene in breast cancer via regulation of cleavage factor “CFIm25”. Scientific Reports, 10(1), 1-11. https://doi.org/10.1038/s41598-020-68406-3
Tan, S., Zhang, M., Shi, X., Ding, K., Zhao, Q., Guo, Q., Wang, H., Wu, Z., Kang, Y., Zhu, T., Sun, J., & Zhao, X. (2021). CPSF6 links alternative polyadenylation to metabolism adaption in hepatocellular carcinoma progression. Journal of Experimental and Clinical Cancer Research, 40(1), 85. https://doi.org/10.1186/S13046-021-01884-Z
Tian, B., & Graber, J. H. (2012). Signals for pre-mRNA cleavage and polyadenylation. Wiley Interdisciplinary Reviews: RNA, 3(3), 385-396. https://doi.org/10.1002/wrna.116
Tian, B., & Manley, J. L. (2016). Alternative polyadenylation of mRNA precursors. Nature Reviews Molecular Cell Biology, 18, 18-30. https://doi.org/10.1038/nrm.2016.116
Turner, R. E., Henneken, L. M., Liem-Weits, M., Harrison, P. F., Swaminathan, A., Vary, R., Nikolic, I., Simpson, K. J., Powell, D. R., Beilharz, T. H., & Dichtl, B. (2020). Requirement for cleavage factor IIm in the control of alternative polyadenylation in breast cancer cells. RNA, 26(8), 969-981. https://doi.org/10.1261/RNA.075226.120
Vallortigara, J., Whitfield, D., Quelch, W., Alghamdi, A., Howlett, D., Hortobágyi, T., Johnson, M., Attems, J., O′Brien, J. T., Thomas, A., Ballard, C. G., Aarsland, D., & Francis, P. T. (2016). Decreased levels of VAMP2 and monomeric alpha-synuclein correlate with duration of dementia. Journal of Alzheimer's Disease, 50(1), 101-110. https://doi.org/10.3233/JAD-150707
Venkataraman, K., Brown, K. M., & Gilmartin, G. M. (2005). Analysis of a noncanonical poly(A) site reveals a tripartite mechanism for vertebrate poly(A) site recognition. Genes and Development, 19(11), 1315-1327. https://doi.org/10.1101/gad.1298605
Wang, R., & Tian, B. (2020). APAlyzer: A bioinformatics package for analysis of alternative polyadenylation isoforms. Bioinformatics, 36(12), 3907-3909. https://doi.org/10.1093/bioinformatics/btaa266
Wang, X., Liu, L., Whisnant, A. W., Hennig, T., Djakovic, L., Haque, N., Bach, C., Sandri-Goldin, R. M., Erhard, F., Friedel, C. C., Dölken, L., & Shi, Y. (2020). Mechanism and consequences of herpes simplex virus 1-mediated regulation of host mRNA alternative polyadenylation. bioRxiv, 17, 1009263. https://doi.org/10.1101/2020.11.26.399626
Wang, Y., Xu, Y., Yan, W., Han, P., Liu, J., Gong, J., Li, D., Ding, X., Wang, H., Lin, Z., Tian, D., & Liao, J. (2018). CFIm25 inhibits hepatocellular carcinoma metastasis by suppressing the p38 and JNK/c-Jun signaling pathways. Oncotarget, 9(14), 11783-11793. https://doi.org/10.18632/oncotarget.24364
Weng, T., Ko, J., Masamha, C. P., Xia, Z., Xiang, Y., Chen, N. Y., Molina, J. G., Collum, S., Mertens, T. C., Luo, F., Philip, K., Davies, J., Huang, J., Wilson, C., Thandavarayan, R. A., Bruckner, B. A., Jyothula, S. S. K., Volcik, K. A., Li, L., & Blackburn, M. R. (2019). Cleavage factor 25 deregulation contributes to pulmonary fibrosis through alternative polyadenylation. Journal of Clinical Investigation, 129(5), 1984-1999. https://doi.org/10.1172/JCI122106
Wong, R. R., Abd-Aziz, N., Affendi, S., & Poh, C. L. (2020). Role of microRNAs in antiviral responses to dengue infection. Journal of Biomedical Science, 27(1), 1-11. https://doi.org/10.1186/s12929-019-0614-x
van Solinge, W. W., Lind, B., van Wijk, R., Herman Ch, H., & Kraaijenhagen, R. J. (1996). Clinical expression of a rare beta-globin gene mutation co-inherited with haemoglobin E-disease. European Journal of Clinical Chemistry and Clinical Biochemistry, 34(12), 949-954. https://doi.org/10.1515/CCLM.1996.34.12.949
Wu, X, Liu, T., Ye, C., Ye, W., & Ji, G. (2020). scAPAtrap: Identification and quantification of alternative polyadenylation sites from single-cell RNA-seq data. Briefings in Bioinformatics, https://doi.org/10.1093/BIB/BBAA273
Yalamanchili, H. K., Alcott, C. E., Ji, P., Wagner, E. J., Zoghbi, H. Y., & Liu, Z. (2020). PolyA-miner: Accurate assessment of differential alternative poly-adenylation from 3′Seq data using vector projections and non-negative matrix factorization. Nucleic Acids Research, 48(12), e69-e69. https://doi.org/10.1093/NAR/GKAA398
Yalamanchili, H. K., Elrod, N. D., Jensen, M. K., Ji, P., Lin, A., Wagner, E. J., & Liu, Z. (2021). A computational pipeline to infer alternative poly-adenylation from 3′ sequencing data. Methods in Enzymology, 655, 185-204. https://doi.org/10.1016/BS.MIE.2021.04.001
Yoon, Y., McKenna, M. C., Rollins, D. A., Song, M., Nuriel, T. Gross, S. S., Xu, G., & Glatt, C. E. (2013). Anxiety-associated alternative polyadenylation of the serotonin transporter mRNA confers translational regulation by hnRNPK. Proceedings of the National Academy of Sciences of the United States of America, 110(28), 11624-11629. https://doi.org/10.1073/pnas.1301485110
Yuan, F., Hankey, W., Wagner, E. J., Li, W., & Wang, Q. (2021). Alternative polyadenylation of mRNA and its role in cancer. Genes & Diseases, 8(1), 61-72. https://doi.org/10.1016/J.GENDIS.2019.10.011
Zarudnaya, M. I., Kolomiets, I. M., Potyahaylo, A. L., & Hovorun, D. M. (2003). Downstream elements of mammalian pre-mRNA polyadenylation signals: Primary, secondary and higher-order structures. Nucleic Acids Research, 31(5), 1375-1386. https://doi.org/10.1093/nar/gkg241
Zhang, S., Zhang, X., Lei, W., Liang, J., Xu, Y., Liu, H., & Ma, S. (2019). Genome-wide profiling reveals alternative polyadenylation of mRNA in human non-small cell lung cancer. Journal of Translational Medicine, 17(1), 257. https://doi.org/10.1186/s12967-019-1986-0
Zhang, Y., Liu, L., Qiu, Q., Zhou, Q., Ding, J., Lu, Y., & Liu, P. (2021). Alternative polyadenylation: Methods, mechanism, function, and role in cancer. Journal of Experimental & Clinical Cancer Research, 40(1), 1-19. https://doi.org/10.1186/S13046-021-01852-7
Zhou, X., Li, X., & Wu, M. (2018). miRNAs reshape immunity and inflammatory responses in bacterial infection. Signal Transduction and Targeted Therapy, 3(1), 14. https://doi.org/10.1038/s41392-018-0006-9
Zhou, Z., Qu, J., He, L., Zhu, Y., Yang, S. Z., Zhang, F., Guo, T., Peng, H., Chen, P., & Zhou, Y. (2020). Stiff matrix instigates type I collagen biogenesis by mammalian cleavage factor I complex-mediated alternative polyadenylation. JCI Insight, 5(3), https://doi.org/10.1172/jci.insight.133972