Alternative cleavage and polyadenylation: extent, regulation and function (original) (raw)
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). ArticleCASPubMed Google Scholar
Sachs, A. The role of poly(A) in the translation and stability of mRNA. Curr. Opin. Cell Biol.2, 1092–1098 (1990). ArticleCASPubMed Google Scholar
Guhaniyogi, J. & Brewer, G. Regulation of mRNA stability in mammalian cells. Gene265, 11–23 (2001). ArticleCASPubMed Google Scholar
D'Ambrogio, A., Nagaoka, K. & Richter, J. D. Translational control of cell growth and malignancy by the CPEBs. Nature Rev. Cancer13, 283–290 (2013). ArticleCAS Google Scholar
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). ArticleCASPubMed Google Scholar
Fabian, M. R., Sonenberg, N. & Filipowicz, W. Regulation of mRNA translation and stability by microRNAs. Annu. Rev. Biochem.79, 351–379 (2010). ArticleCASPubMed Google Scholar
Andreassi, C. & Riccio, A. To localize or not to localize: mRNA fate is in 3′UTR ends. Trends Cell Biol.19, 465–474 (2009). ArticleCASPubMed Google Scholar
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). ArticleCASPubMed Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar
Brown, K. M. & Gilmartin, G. M. A mechanism for the regulation of pre-mRNA 3′ processing by human cleavage factor Im. Mol. Cell12, 1467–1476 (2003). ArticleCASPubMed Google Scholar
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. Science320, 1643–1647 (2008). This paper presents the first genomic demonstration of the association between APA and proliferation. ArticleCASPubMedPubMed Central Google Scholar
Pickrell, J. K. et al. Understanding mechanisms underlying human gene expression variation with RNA sequencing. Nature464, 768–772 (2010). ArticleCASPubMedPubMed Central Google Scholar
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). ArticleCASPubMed Google Scholar
Hoque, M. et al. Analysis of alternative cleavage and polyadenylation by 3′ region extraction and deep sequencing. Nature Methods10, 133–139 (2012). ArticlePubMedPubMed CentralCAS Google Scholar
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. USA106, 7028–7033 (2009). ArticleCASPubMedPubMed Central Google Scholar
Hilgers, V. et al. Neural-specific elongation of 3′ UTRs during Drosophila development. Proc. Natl Acad. Sci. USA108, 15864–15869 (2011). ArticleCASPubMedPubMed Central Google Scholar
Ji, Z. & Tian, B. Reprogramming of 3′ untranslated regions of mRNAs by alternative polyadenylation in generation of pluripotent stem cells from different cell types. PLoS ONE4, e8419 (2009). ArticlePubMedPubMed CentralCAS Google Scholar
Timmusk, T. et al. Multiple promoters direct tissue-specific expression of the rat BDNF gene. Neuron10, 475–489 (1993). ArticleCASPubMed Google Scholar
Lau, A. G. et al. Distinct 3′UTRs differentially regulate activity-dependent translation of brain-derived neurotrophic factor (BDNF). Proc. Natl Acad. Sci. USA107, 15945–15950 (2010). ArticleCASPubMedPubMed Central Google Scholar
Flavell, S. W. et al. Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection. Neuron60, 1022–1038 (2008). ArticleCASPubMedPubMed Central Google Scholar
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. Cell2, 761–771 (1998). ArticleCASPubMed Google Scholar
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. Cell87, 941–952 (1996). ArticleCASPubMed Google Scholar
Yao, C. et al. Transcriptome-wide analyses of CstF64–RNA interactions in global regulation of mRNA alternative polyadenylation. Proc. Natl Acad. Sci. USA109, 18773–18778 (2012). ArticleCASPubMedPubMed Central Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar
Kim, S. et al. Evidence that cleavage factor Im is a heterotetrameric protein complex controlling alternative polyadenylation. Genes Cells15, 1003–1013 (2010). ArticleCASPubMed Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar
Maniatis, T. & Reed, R. An extensive network of coupling among gene expression machines. Nature416, 499–506 (2002). ArticleCASPubMed Google Scholar
Perales, R. & Bentley, D. “Cotranscriptionality”: the transcription elongation complex as a nexus for nuclear transactions. Mol. Cell36, 178–191 (2009). ArticleCASPubMedPubMed Central Google Scholar
Di Giammartino, D. C., Nishida, K. & Manley, J. L. Mechanisms and consequences of alternative polyadenylation. Mol. Cell43, 853–866 (2011). ArticleCASPubMedPubMed Central Google Scholar
Rozenblatt-Rosen, O. et al. The tumor suppressor CDC73 functionally associates with CPSF and CstF 3′ mRNA processing factors. Proc. Natl Acad. Sci. USA106, 755–760 (2009). ArticleCASPubMedPubMed Central Google Scholar
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). ArticleCAS Google Scholar
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. ArticlePubMedPubMed CentralCAS Google Scholar
de la Mata, M. et al. A slow RNA polymerase II affects alternative splicing in vivo. Mol. Cell12, 525–532 (2003). ArticleCASPubMed Google Scholar
Spies, N., Nielsen, C. B., Padgett, R. A. & Burge, C. B. Biased chromatin signatures around polyadenylation sites and exons. Mol. Cell36, 245–254 (2009). ArticleCASPubMedPubMed Central Google Scholar
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). ArticlePubMedPubMed CentralCAS Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar
Millevoi, S. & Vagner, S. Molecular mechanisms of eukaryotic pre-mRNA 3′ end processing regulation. Nucleic Acids Res.38, 2757–2774 (2010). ArticleCASPubMed Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar
Berg, M. G. et al. U1 snRNP determines mRNA length and regulates isoform expression. Cell150, 53–64 (2012). This paper characterizes the role of U1 in the interplay between APA and splicing. ArticleCASPubMedPubMed Central Google Scholar
Jenal, M. et al. The poly(A)-binding protein nuclear 1 suppresses alternative cleavage and polyadenylation sites. Cell149, 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. ArticleCASPubMed Google Scholar
de Klerk, E. et al. Poly(A) binding protein nuclear 1 levels affect alternative polyadenylation. Nucleic Acids Res.40, 9089–9101 (2012). ArticlePubMedPubMed CentralCAS Google Scholar
Hilgers, V., Lemke, S. B. & Levine, M. ELAV mediates 3′ UTR extension in the Drosophila nervous system. Genes Dev.26, 2259–2264 (2012). ArticleCASPubMedPubMed Central Google Scholar
Mansfield, K. D. & Keene, J. D. Neuron-specific ELAV/Hu proteins suppress HuR mRNA during neuronal differentiation by alternative polyadenylation. Nucleic Acids Res.40, 2734–2746 (2012). ArticleCASPubMed Google Scholar
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). ArticleCASPubMed Google Scholar
Castelo-Branco, P. et al. Polypyrimidine tract binding protein modulates efficiency of polyadenylation. Mol. Cell. Biol.24, 4174–4183 (2004). ArticleCASPubMedPubMed Central Google Scholar
Danckwardt, S. et al. Splicing factors stimulate polyadenylation via USEs at non-canonical 3′ end formation signals. EMBO J.26, 2658–2669 (2007). ArticleCASPubMedPubMed Central Google Scholar
Bava, F. A. et al. CPEB1 coordinates alternative 3′-UTR formation with translational regulation. Nature495, 121–125 (2013). This paper shows that CPEB1, which is the key regulator of cytoplasmic polyadenylation, also regulates nuclear APA. ArticleCASPubMed Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar
Park, J. Y. et al. Comparative analysis of mRNA isoform expression in cardiac hypertrophy and development reveals multiple post-transcriptional regulatory modules. PLoS ONE6, e22391 (2011). ArticleCASPubMedPubMed Central Google Scholar
Mayr, C. & Bartel, D. P. Widespread shortening of 3′UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell138, 673–684 (2009). This paper is the first to demonstrate an association between enhanced APA and cancer. ArticleCASPubMedPubMed Central Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar
Morris, A. R. et al. Alternative cleavage and polyadenylation during colorectal cancer development. Clin. Cancer Res.18, 5256–5266 (2012). ArticleCASPubMed Google Scholar
Galluzzi, L. et al. Prognostic impact of vitamin B6 metabolism in lung cancer. Cell Rep.2, 257–269 (2012). ArticleCASPubMed Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar
Vorlova, S. et al. Induction of antagonistic soluble decoy receptor tyrosine kinases by intronic polyA activation. Mol. Cell43, 927–939 (2011). This is the first demonstration, to our knowledge, of the therapeutic potential for external manipulation of APA. ArticleCASPubMedPubMed Central Google Scholar
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). ArticleCAS Google Scholar
Kole, R., Krainer, A. R. & Altman, S. RNA therapeutics: beyond RNA interference and antisense oligonucleotides. Nature Rev. Drug Discov.11, 125–140 (2012). ArticleCAS Google Scholar
Yoon, O. K. & Brem, R. B. Noncanonical transcript forms in yeast and their regulation during environmental stress. RNA16, 1256–1267 (2010). ArticleCASPubMedPubMed Central Google Scholar
Jan, C. H., Friedman, R. C., Ruby, J. G. & Bartel, D. P. Formation, regulation and evolution of Caenorhabditis elegans 3′UTRs. Nature469, 97–101 (2011). ArticleCASPubMed Google Scholar
Ozsolak, F. et al. Comprehensive polyadenylation site maps in yeast and human reveal pervasive alternative polyadenylation. Cell143, 1018–1029 (2010). ArticleCASPubMedPubMed Central Google Scholar
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). ArticlePubMedPubMed CentralCAS Google Scholar
Colgan, D. F. & Manley, J. L. Mechanism and regulation of mRNA polyadenylation. Genes Dev.11, 2755–2766 (1997). ArticleCASPubMed Google Scholar
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. Structure19, 368–377 (2011). ArticleCASPubMedPubMed Central Google Scholar
Higgs, D. R. et al. Alpha-thalassaemia caused by a polyadenylation signal mutation. Nature306, 398–400 (1983). ArticleCASPubMed Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar
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. USA86, 9436–9440 (1989). ArticleCASPubMedPubMed Central Google Scholar
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). ArticleCASPubMed Google Scholar
Bennett, C. L. et al. A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA–>AAUGAA) leads to the IPEX syndrome. Immunogenetics53, 435–439 (2001). ArticleCASPubMed Google Scholar
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). ArticleCASPubMedPubMed Central Google Scholar