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Alternative cleavage and polyadenylation: extent, regulation and function

Elkon, Ran, Ugalde, Alejandro P., Agami, Reuven·2013·Nature Reviews Genetics
DOI 10.1038/nrg3482
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  1. Edmonds, M. & Abrams, R. Polynucleotide biosynthesis: formation of a sequence of adenylate units from adenosine triphosphate by an enzyme from thymus nuclei. J. Biol. Chem. 235, 1142–1149 (1960). · DOI
  2. Proudfoot, N. J. Ending the message: poly(A) signals then and now. Genes Dev. 25, 1770–1782 (2011). · DOI · Paper page
  3. Sachs, A. The role of poly(A) in the translation and stability of mRNA. Curr. Opin. Cell Biol. 2, 1092–1098 (1990). · DOI · Paper page
  4. Guhaniyogi, J. & Brewer, G. Regulation of mRNA stability in mammalian cells. Gene 265, 11–23 (2001). · DOI · Paper page
  5. D'Ambrogio, A., Nagaoka, K. & Richter, J. D. Translational control of cell growth and malignancy by the CPEBs. Nature Rev. Cancer 13, 283–290 (2013). · DOI
  6. Martin, G., Gruber, A. R., Keller, W. & Zavolan, M. Genome-wide analysis of pre-mRNA 3′ end processing reveals a decisive role of human cleavage factor I in the regulation of 3′ UTR length. Cell Rep. 1, 753–763 (2012). · DOI · Paper page
  7. Andreassi, C. & Riccio, A. To localize or not to localize: mRNA fate is in 3′UTR ends. Trends Cell Biol. 19, 465–474 (2009). · DOI · Paper page
  8. Gautheret, D., Poirot, O., Lopez, F., Audic, S. & Claverie, J. M. Alternate polyadenylation in human mRNAs: a large-scale analysis by EST clustering. Genome Res. 8, 524–530 (1998). · DOI
  9. Beaudoing, E., Freier, S., Wyatt, J. R., Claverie, J. M. & Gautheret, D. Patterns of variant polyadenylation signal usage in human genes. Genome Res. 10, 1001–1010 (2000). · DOI · Paper page
  10. Tian, B., Hu, J., Zhang, H. & Lutz, C. S. A large-scale analysis of mRNA polyadenylation of human and mouse genes. Nucleic Acids Res. 33, 201–212 (2005). · DOI · Paper page
  11. Brown, K. M. & Gilmartin, G. M. A mechanism for the regulation of pre-mRNA 3′ processing by human cleavage factor Im. Mol. Cell 12, 1467–1476 (2003). · DOI · Paper page
  12. Sandberg, R., Neilson, J. R., Sarma, A., Sharp, P. A. & Burge, C. B. Proliferating cells express mRNAs with shortened 3′ untranslated regions and fewer microRNA target sites. Science 320, 1643–1647 (2008). This paper presents the first genomic demonstration of the association between APA and proliferation. · DOI · Paper page
  13. Sun, Y., Fu, Y., Li, Y. & Xu, A. Genome-wide alternative polyadenylation in animals: insights from high-throughput technologies. J. Mol. Cell. Biol. 4, 352–361 (2012). · DOI
  14. Hoque, M. et al. Analysis of alternative cleavage and polyadenylation by 3′ region extraction and deep sequencing. Nature Methods 10, 133–139 (2012). · DOI · Paper page
  15. Zhang, H., Lee, J. Y. & Tian, B. Biased alternative polyadenylation in human tissues. Genome Biol. 6, R100 (2005). · DOI · Paper page
  16. Ji, Z., Lee, J. Y., Pan, Z., Jiang, B. & Tian, B. Progressive lengthening of 3′ untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development. Proc. Natl Acad. Sci. USA 106, 7028–7033 (2009). · DOI · Paper page
  17. Hilgers, V. et al. Neural-specific elongation of 3′ UTRs during Drosophila development. Proc. Natl Acad. Sci. USA 108, 15864–15869 (2011). · DOI
  18. Shepard, P. J. et al. Complex and dynamic landscape of RNA polyadenylation revealed by PAS-seq. RNA 17, 761–772 (2011). · DOI · Paper page
  19. Smibert, P. et al. Global patterns of tissue-specific alternative polyadenylation in Drosophila. Cell Rep. 1, 277–289 (2012). · DOI · Paper page
  20. Ulitsky, I. et al. Extensive alternative polyadenylation during zebrafish development. Genome Res. 22, 2054–2066 (2012). · DOI · Paper page
  21. Elkon, R. et al. E2F mediates enhanced alternative polyadenylation in proliferation. Genome Biol. 13, R59 (2012). · DOI
  22. Timmusk, T. et al. Multiple promoters direct tissue-specific expression of the rat BDNF gene. Neuron 10, 475–489 (1993). · DOI · Paper page
  23. Lau, A. G. et al. Distinct 3′UTRs differentially regulate activity-dependent translation of brain-derived neurotrophic factor (BDNF). Proc. Natl Acad. Sci. USA 107, 15945–15950 (2010). · DOI · Paper page
  24. Takagaki, Y. & Manley, J. L. Levels of polyadenylation factor CstF-64 control IgM heavy chain mRNA accumulation and other events associated with B cell differentiation. Mol. Cell 2, 761–771 (1998). · DOI · Paper page
  25. Takagaki, Y., Seipelt, R. L., Peterson, M. L. & Manley, J. L. The polyadenylation factor CstF-64 regulates alternative processing of IgM heavy chain pre-mRNA during B cell differentiation. Cell 87, 941–952 (1996). · DOI · Paper page
  26. Yao, C. et al. Transcriptome-wide analyses of CstF64–RNA interactions in global regulation of mRNA alternative polyadenylation. Proc. Natl Acad. Sci. USA 109, 18773–18778 (2012). · DOI · Paper page
  27. Kubo, T., Wada, T., Yamaguchi, Y., Shimizu, A. & Handa, H. Knock-down of 25 kDa subunit of cleavage factor Im in Hela cells alters alternative polyadenylation within 3′-UTRs. Nucleic Acids Res. 34, 6264–6271 (2006). · DOI
  28. Kim, S. et al. Evidence that cleavage factor Im is a heterotetrameric protein complex controlling alternative polyadenylation. Genes Cells 15, 1003–1013 (2010). · DOI
  29. Venkataraman, K., Brown, K. M. & Gilmartin, G. M. Analysis of a noncanonical poly(A) site reveals a tripartite mechanism for vertebrate poly(A) site recognition. Genes Dev. 19, 1315–1327 (2005). · DOI · Paper page
  30. Nunes, N. M., Li, W., Tian, B. & Furger, A. A functional human poly(A) site requires only a potent DSE and an A-rich upstream sequence. EMBO J. 29, 1523–1536 (2010). · DOI
  31. Maniatis, T. & Reed, R. An extensive network of coupling among gene expression machines. Nature 416, 499–506 (2002). · DOI · Paper page
  32. Perales, R. & Bentley, D. “Cotranscriptionality”: the transcription elongation complex as a nexus for nuclear transactions. Mol. Cell 36, 178–191 (2009). · DOI · Paper page
  33. Shi, Y. et al. Molecular architecture of the human pre-mRNA 3′ processing complex. Mol. Cell 33, 365–376 (2009). · DOI · Paper page
  34. Nagaike, T. et al. Transcriptional activators enhance polyadenylation of mRNA precursors. Mol. Cell 41, 409–418 (2011). · DOI
  35. Rozenblatt-Rosen, O. et al. The tumor suppressor CDC73 functionally associates with CPSF and CstF 3′ mRNA processing factors. Proc. Natl Acad. Sci. USA 106, 755–760 (2009). · DOI
  36. Martincic, K., Alkan, S. A., Cheatle, A., Borghesi, L. & Milcarek, C. Transcription elongation factor ELL2 directs immunoglobulin secretion in plasma cells by stimulating altered RNA processing. Nature Immunol. 10, 1102–1109 (2009). · DOI
  37. Ji, Z. et al. Transcriptional activity regulates alternative cleavage and polyadenylation. Mol. Syst. Biol. 7, 534 (2011). This paper provides a nice demonstration of the interplay between APA and transcription. · DOI
  38. Pinto, P. A. et al. RNA polymerase II kinetics in polo polyadenylation signal selection. EMBO J. 30, 2431–2444 (2011). · DOI · Paper page
  39. de la Mata, M. et al. A slow RNA polymerase II affects alternative splicing in vivo. Mol. Cell 12, 525–532 (2003). · DOI · Paper page
  40. Spies, N., Nielsen, C. B., Padgett, R. A. & Burge, C. B. Biased chromatin signatures around polyadenylation sites and exons. Mol. Cell 36, 245–254 (2009). · DOI
  41. Wood, A. J. et al. A screen for retrotransposed imprinted genes reveals an association between X chromosome homology and maternal germ-line methylation. PLoS Genet. 3, e20 (2007). · DOI
  42. Cowley, M., Wood, A. J., Bohm, S., Schulz, R. & Oakey, R. J. Epigenetic control of alternative mRNA processing at the imprinted Herc3/Nap1l5 locus. Nucleic Acids Res. 40, 8917–8926 (2012). · DOI
  43. Millevoi, S. et al. An interaction between U2AF 65 and CF I(m) links the splicing and 3′ end processing machineries. EMBO J. 25, 4854–4864 (2006). · DOI · Paper page
  44. Millevoi, S. & Vagner, S. Molecular mechanisms of eukaryotic pre-mRNA 3′ end processing regulation. Nucleic Acids Res. 38, 2757–2774 (2010). · DOI · Paper page
  45. Tian, B., Pan, Z. & Lee, J. Y. Widespread mRNA polyadenylation events in introns indicate dynamic interplay between polyadenylation and splicing. Genome Res. 17, 156–165 (2007). · DOI · Paper page
  46. Berg, M. G. et al. U1 snRNP determines mRNA length and regulates isoform expression. Cell 150, 53–64 (2012). This paper characterizes the role of U1 in the interplay between APA and splicing. · DOI · Paper page
  47. Jenal, M. et al. The poly(A)-binding protein nuclear 1 suppresses alternative cleavage and polyadenylation sites. Cell 149, 538–553 (2012). This paper identifies PABPN1 as a regulator of APA and provides the first link between a human genetic disorder (specifically, OPMD) and broad APA misregulation. · DOI · Paper page
  48. de Klerk, E. et al. Poly(A) binding protein nuclear 1 levels affect alternative polyadenylation. Nucleic Acids Res. 40, 9089–9101 (2012). · DOI · Paper page
  49. Hilgers, V., Lemke, S. B. & Levine, M. ELAV mediates 3′ UTR extension in the Drosophila nervous system. Genes Dev. 26, 2259–2264 (2012). · DOI
  50. Zhu, H., Zhou, H. L., Hasman, R. A. & Lou, H. Hu proteins regulate polyadenylation by blocking sites containing U-rich sequences. J. Biol. Chem. 282, 2203–2210 (2007). · DOI
  51. Castelo-Branco, P. et al. Polypyrimidine tract binding protein modulates efficiency of polyadenylation. Mol. Cell. Biol. 24, 4174–4183 (2004). · DOI · Paper page
  52. Danckwardt, S. et al. Splicing factors stimulate polyadenylation via USEs at non-canonical 3′ end formation signals. EMBO J. 26, 2658–2669 (2007). · DOI
  53. Bava, F. A. et al. CPEB1 coordinates alternative 3′-UTR formation with translational regulation. Nature 495, 121–125 (2013). This paper shows that CPEB1, which is the key regulator of cytoplasmic polyadenylation, also regulates nuclear APA. · DOI · Paper page
  54. Danckwardt, S., Hentze, M. W. & Kulozik, A. E. 3′ end mRNA processing: molecular mechanisms and implications for health and disease. EMBO J. 27, 482–498 (2008). · DOI · Paper page
  55. Park, J. Y. et al. Comparative analysis of mRNA isoform expression in cardiac hypertrophy and development reveals multiple post-transcriptional regulatory modules. PLoS ONE 6, e22391 (2011). · DOI
  56. Fu, Y. et al. Differential genome-wide profiling of tandem 3′ UTRs among human breast cancer and normal cells by high-throughput sequencing. Genome Res. 21, 741–747 (2011). · DOI · Paper page
  57. Lin, Y. et al. An in-depth map of polyadenylation sites in cancer. Nucleic Acids Res. 40, 8460–8471 (2012). · DOI
  58. Morris, A. R. et al. Alternative cleavage and polyadenylation during colorectal cancer development. Clin. Cancer Res. 18, 5256–5266 (2012). · DOI
  59. Galluzzi, L. et al. Prognostic impact of vitamin B6 metabolism in lung cancer. Cell Rep. 2, 257–269 (2012). · DOI
  60. Akman, B. H., Can, T. & Erson-Bensan, A. E. Estrogen-induced upregulation and 3′-UTR shortening of CDC6. Nucleic Acids Res. 40, 10679–10688 (2012). · DOI
  61. Vorlova, S. et al. Induction of antagonistic soluble decoy receptor tyrosine kinases by intronic polyA activation. Mol. Cell 43, 927–939 (2011). This is the first demonstration, to our knowledge, of the therapeutic potential for external manipulation of APA. · DOI
  62. Ingolia, N. T., Brar, G. A., Rouskin, S., McGeachy, A. M. & Weissman, J. S. The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments. Nature Protoc. 7, 1534–1550 (2012). · DOI · Paper page
  63. Kole, R., Krainer, A. R. & Altman, S. RNA therapeutics: beyond RNA interference and antisense oligonucleotides. Nature Rev. Drug Discov. 11, 125–140 (2012). · DOI · Paper page
  64. Yoon, O. K. & Brem, R. B. Noncanonical transcript forms in yeast and their regulation during environmental stress. RNA 16, 1256–1267 (2010). · DOI
  65. Derti, A. et al. A quantitative atlas of polyadenylation in five mammals. Genome Res. 22, 1173–1183 (2012). · DOI · Paper page
  66. Beck, A. H. et al. 3′-end sequencing for expression quantification (3SEQ) from archival tumor samples. PLoS ONE 5, e8768 (2010). · DOI
  67. Jan, C. H., Friedman, R. C., Ruby, J. G. & Bartel, D. P. Formation, regulation and evolution of Caenorhabditis elegans 3′UTRs. Nature 469, 97–101 (2011). · DOI · Paper page
  68. Ozsolak, F. et al. Comprehensive polyadenylation site maps in yeast and human reveal pervasive alternative polyadenylation. Cell 143, 1018–1029 (2010). · DOI · Paper page
  69. Friedel, C. C., Dolken, L., Ruzsics, Z., Koszinowski, U. H. & Zimmer, R. Conserved principles of mammalian transcriptional regulation revealed by RNA half-life. Nucleic Acids Res. 37, e115 (2009). · DOI · Paper page
  70. Mandel, C. R., Bai, Y. & Tong, L. Protein factors in pre-mRNA 3′-end processing. Cell. Mol. Life Sci. 65, 1099–1122 (2008). · DOI · Paper page
  71. Yang, Q., Coseno, M., Gilmartin, G. M. & Doublie, S. Crystal structure of a human cleavage factor CFI(m)25/CFI(m)68/RNA complex provides an insight into poly(A) site recognition and RNA looping. Structure 19, 368–377 (2011). · DOI
  72. Higgs, D. R. et al. Alpha-thalassaemia caused by a polyadenylation signal mutation. Nature 306, 398–400 (1983). · DOI · Paper page
  73. Orkin, S. H., Cheng, T. C., Antonarakis, S. E. & Kazazian, H. H. Jr. Thalassemia due to a mutation in the cleavage-polyadenylation signal of the human β-globin gene. EMBO J. 4, 453–456 (1985). · DOI · Paper page
  74. Gieselmann, V., Polten, A., Kreysing, J. & von Figura, K. Arylsulfatase A pseudodeficiency: loss of a polyadenylylation signal and N-glycosylation site. Proc. Natl Acad. Sci. USA 86, 9436–9440 (1989). · DOI · Paper page
  75. Barth, M. L., Fensom, A. & Harris, A. Prevalence of common mutations in the arylsulphatase A gene in metachromatic leukodystrophy patients diagnosed in Britain. Hum. Genet. 91, 73–77 (1993). · DOI
  76. Bennett, C. L. et al. A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA–>AAUGAA) leads to the IPEX syndrome. Immunogenetics 53, 435–439 (2001). · DOI · Paper page
  77. Yasuda, M., Shabbeer, J., Osawa, M. & Desnick, R. J. Fabry disease: novel α-galactosidase A 3′-terminal mutations result in multiple transcripts due to aberrant 3′-end formation. Am. J. Hum. Genet. 73, 162–173 (2003). · DOI

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Metadata

Authors
Elkon, R., Ugalde, A. P., & Agami, R.
Venue
Nature Reviews Genetics
Publisher
Springer Science and Business Media LLC
Published
2013-06-18
Volume
14
Issue
7
Pages
496-506
ISSN
  • 1471-0056 (ISSN-L)
  • 1471-0064
DOI
10.1038/nrg3482
OpenAlex
W1985267020
Cited by
804
References
12
FWCI
4.14
Type
journal article
Language
en
Open access
closed
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