Alternative polyadenylation of mRNA and its role in cancer

Crick, 1970, Central dogma of molecular biology, Nature, 227, 561, 10.1038/227561a0 Elkon, 2013, Alternative cleavage and polyadenylation: extent, regulation and function, Nat Rev Genet, 14, 496, 10.1038/nrg3482 Gruber, 2019, Alternative cleavage and polyadenylation in health and disease, Nat Rev Genet, 20, 599, 10.1038/s41576-019-0145-z Mayr, 2019, What are 3’ UTRs doing?, Cold Spring Harb Perspect Biol, 11, 10.1101/cshperspect.a034728 Tian, 2017, Alternative polyadenylation of mRNA precursors, Nat Rev Mol Cell Biol, 18, 18, 10.1038/nrm.2016.116 Tian, 2005, A large-scale analysis of mRNA polyadenylation of human and mouse genes, Nucleic Acids Res, 33, 201, 10.1093/nar/gki158 Beaudoing, 2001, Identification of alternate polyadenylation sites and analysis of their tissue distribution using EST data, Genome Res, 11, 1520, 10.1101/gr.190501 Venkataraman, 2005, Analysis of a noncanonical poly(A) site reveals a tripartite mechanism for vertebrate poly(A) site recognition, Genes Dev, 19, 1315, 10.1101/gad.1298605 Takagaki, 1997, RNA recognition by the human polyadenylation factor CstF, Mol Cell Biol, 17, 3907, 10.1128/MCB.17.7.3907 Chen, 1998, Auxiliary downstream elements are required for efficient polyadenylation of mammalian pre-mRNAs, Nucleic Acids Res, 26, 2891, 10.1093/nar/26.12.2891 Shi, 2009, Molecular architecture of the human pre-mRNA 3' processing complex, Mol Cell, 33, 365, 10.1016/j.molcel.2008.12.028 Murthy, 1995, The 160-kD subunit of human cleavage-polyadenylation specificity factor coordinates pre-mRNA 3'-end formation, Genes Dev, 9, 2672, 10.1101/gad.9.21.2672 Kaufmann, 2004, Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase, EMBO J, 23, 616, 10.1038/sj.emboj.7600070 Derti, 2012, A quantitative atlas of polyadenylation in five mammals, Genome Res, 22, 1173, 10.1101/gr.132563.111 Shi, 2012, Alternative polyadenylation: new insights from global analyses, RNA, 18, 2105, 10.1261/rna.035899.112 Wang, 2018, A compendium of conserved cleavage and polyadenylation events in mammalian genes, Genome Res, 28, 1427, 10.1101/gr.237826.118 Reyes, 2018, Alternative start and termination sites of transcription drive most transcript isoform differences across human tissues, Nucleic Acids Res, 46, 582, 10.1093/nar/gkx1165 Chang, 2018, Dynamics of alternative polyadenylation in human preimplantation embryos, Biochem Biophys Res Commun, 504, 727, 10.1016/j.bbrc.2018.09.027 Hu, 2017, Dynamic landscape of alternative polyadenylation during retinal development, Cell Mol Life Sci, 74, 1721, 10.1007/s00018-016-2429-1 Zhou, 2019, Alternative polyadenylation coordinates embryonic development, sexual dimorphism and longitudinal growth in Xenopus tropicalis, Cell Mol Life Sci, 76, 2185, 10.1007/s00018-019-03036-1 Sadek, 2019, Alternative polyadenylation and the stress response, Wiley Interdiscipl Rev RNA, 10, 10.1002/wrna.1540 Hoque, 2013, Analysis of alternative cleavage and polyadenylation by 3' region extraction and deep sequencing, Nat Methods, 10, 133, 10.1038/nmeth.2288 Sandberg, 2008, Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites, Science, 320, 1643, 10.1126/science.1155390 Ji, 2009, Reprogramming of 3' untranslated regions of mRNAs by alternative polyadenylation in generation of pluripotent stem cells from different cell types, PLoS One, 4, 10.1371/journal.pone.0008419 Mayr, 2016, Evolution and biological roles of alternative 3'UTRs, Trends Cell Biol, 26, 227, 10.1016/j.tcb.2015.10.012 Mayr, 2009, Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells, Cell, 138, 673, 10.1016/j.cell.2009.06.016 Xia, 2014, Dynamic analyses of alternative polyadenylation from RNA-seq reveal a 3'-UTR landscape across seven tumour types, Nat Commun, 5, 10.1038/ncomms6274 Hilgers, 2011, Neural-specific elongation of 3' UTRs during Drosophila development, Proc Natl Acad Sci U S A, 108, 15864, 10.1073/pnas.1112672108 Ji, 2009, Progressive lengthening of 3' untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development, Proc Natl Acad Sci U S A, 106, 7028, 10.1073/pnas.0900028106 Lee, 2018, Widespread intronic polyadenylation inactivates tumour suppressor genes in leukaemia, Nature, 561, 127, 10.1038/s41586-018-0465-8 Singh, 2009, Global changes in processing of mRNA 3' untranslated regions characterize clinically distinct cancer subtypes, Cancer Res, 69, 9422, 10.1158/0008-5472.CAN-09-2236 Fu, 2011, Differential genome-wide profiling of tandem 3' UTRs among human breast cancer and normal cells by high-throughput sequencing, Genome Res, 21, 741, 10.1101/gr.115295.110 Masamha, 2014, CFIm25 links alternative polyadenylation to glioblastoma tumour suppression, Nature, 510, 412, 10.1038/nature13261 Turner, 2018, Alternative polyadenylation in the regulation and dysregulation of gene expression, Semin Cell Dev Biol, 75, 61, 10.1016/j.semcdb.2017.08.056 Li, 2015, Systematic profiling of poly(A)+ transcripts modulated by core 3' end processing and splicing factors reveals regulatory rules of alternative cleavage and polyadenylation, PLoS Genet, 11, 10.1371/journal.pgen.1005166 Tian, 2007, Widespread mRNA polyadenylation events in introns indicate dynamic interplay between polyadenylation and splicing, Genome Res, 17, 156, 10.1101/gr.5532707 Li, 2017, Interplay between alternative splicing and alternative polyadenylation defines the expression outcome of the plant unique OXIDATIVE TOLERANT-6 gene, Sci Rep, 7, 2052, 10.1038/s41598-017-02215-z Berkovits, 2015, Alternative 3' UTRs act as scaffolds to regulate membrane protein localization, Nature, 522, 363, 10.1038/nature14321 Hoffman, 2016, 3'UTR shortening potentiates MicroRNA-based repression of pro-differentiation genes in proliferating human cells, PLoS Genet, 12, 10.1371/journal.pgen.1005879 Taliaferro, 2016, Distal alternative last exons localize mRNAs to neural projections, Mol Cell, 61, 821, 10.1016/j.molcel.2016.01.020 Lau, 2010, Distinct 3'UTRs differentially regulate activity-dependent translation of brain-derived neurotrophic factor (BDNF), Proc Natl Acad Sci U S A, 107, 15945, 10.1073/pnas.1002929107 Chu, 2019, Nudt21 regulates the alternative polyadenylation of Pak1 and is predictive in the prognosis of glioblastoma patients, Oncogene, 38, 4154, 10.1038/s41388-019-0714-9 Proudfoot, 2011, Ending the message: poly(A) signals then and now, Genes Dev, 25, 1770, 10.1101/gad.17268411 Sun, 2018, Molecular basis for the recognition of the human AAUAAA polyadenylation signal, Proc Natl Acad Sci U S A, 115, E1419, 10.1073/pnas.1718723115 Clerici, 2018, Structural basis of AAUAAA polyadenylation signal recognition by the human CPSF complex, Nat Struct Mol Biol, 25, 135, 10.1038/s41594-017-0020-6 Casanal, 2017, Architecture of eukaryotic mRNA 3'-end processing machinery, Science, 358, 1056, 10.1126/science.aao6535 Hu, 2005, Bioinformatic identification of candidate cis-regulatory elements involved in human mRNA polyadenylation, RNA, 11, 1485, 10.1261/rna.2107305 MacDonald, 2002, Reexamining the polyadenylation signal: were we wrong about AAUAAA?, Mol Cell Endocrinol, 190, 1, 10.1016/S0303-7207(02)00044-8 Tian, 2012, Signals for pre-mRNA cleavage and polyadenylation, Wiley Interdiscipl Rev RNA, 3, 385, 10.1002/wrna.116 Gruber, 2016, A comprehensive analysis of 3' end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogeneous ribonucleoprotein C on cleavage and polyadenylation, Genome Res, 26, 1145, 10.1101/gr.202432.115 Dantonel, 1997, Transcription factor TFIID recruits factor CPSF for formation of 3' end of mRNA, Nature, 389, 399, 10.1038/38763 Mandel, 2006, Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease, Nature, 444, 953, 10.1038/nature05363 Gil, 1987, Position-dependent sequence elements downstream of AAUAAA are required for efficient rabbit beta-globin mRNA 3' end formation, Cell, 49, 399, 10.1016/0092-8674(87)90292-3 Cheng, 2006, Prediction of mRNA polyadenylation sites by support vector machine, Bioinformatics, 22, 2320, 10.1093/bioinformatics/btl394 Murthy, 1992, Characterization of the multisubunit cleavage-polyadenylation specificity factor from calf thymus, J Biol Chem, 267, 14804, 10.1016/S0021-9258(18)42111-4 Clerici, 2017, Structural insights into the assembly and polyA signal recognition mechanism of the human CPSF complex, Elife, 6, 10.7554/eLife.33111 Chan, 2014, CPSF30 and Wdr33 directly bind to AAUAAA in mammalian mRNA 3' processing, Genes Dev, 28, 2370, 10.1101/gad.250993.114 Schonemann, 2014, Reconstitution of CPSF active in polyadenylation: recognition of the polyadenylation signal by WDR33, Genes Dev, 28, 2381, 10.1101/gad.250985.114 Grozdanov, 2018, The structural basis of CstF-77 modulation of cleavage and polyadenylation through stimulation of CstF-64 activity, Nucleic Acids Res, 46, 12022 Lackford, 2014, Fip1 regulates mRNA alternative polyadenylation to promote stem cell self-renewal, EMBO J, 33, 878, 10.1002/embj.201386537 Shankarling, 2009, A family of splice variants of CstF-64 expressed in vertebrate nervous systems, BMC Mol Biol, 10, 10.1186/1471-2199-10-22 Takagaki, 2000, Complex protein interactions within the human polyadenylation machinery identify a novel component, Mol Cell Biol, 20, 1515, 10.1128/MCB.20.5.1515-1525.2000 Moreno-Morcillo, 2011, Locked tether formation by cooperative folding of Rna14p monkeytail and Rna15p hinge domains in the yeast CF IA complex, Structure, 19, 534, 10.1016/j.str.2011.02.003 Bai, 2007, Crystal structure of murine CstF-77: dimeric association and implications for polyadenylation of mRNA precursors, Mol Cell, 25, 863, 10.1016/j.molcel.2007.01.034 Yao, 2012, Transcriptome-wide analyses of CstF64-RNA interactions in global regulation of mRNA alternative polyadenylation, Proc Natl Acad Sci U S A, 109, 18773, 10.1073/pnas.1211101109 Brown, 2003, A mechanism for the regulation of pre-mRNA 3' processing by human cleavage factor Im, Mol Cell, 12, 1467, 10.1016/S1097-2765(03)00453-2 Coseno, 2008, Crystal structure of the 25 kDa subunit of human cleavage factor Im, Nucleic Acids Res, 36, 3474, 10.1093/nar/gkn079 Yang, 2010, Structural basis of UGUA recognition by the Nudix protein CFI(m)25 and implications for a regulatory role in mRNA 3' processing, Proc Natl Acad Sci U S A, 107, 10062, 10.1073/pnas.1000848107 Ruegsegger, 1996, Purification and characterization of human cleavage factor Im involved in the 3' end processing of messenger RNA precursors, J Biol Chem, 271, 6107, 10.1074/jbc.271.11.6107 Martin, 2012, 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, 10.1016/j.celrep.2012.05.003 Zhu, 2018, Molecular mechanisms for CFIm-mediated regulation of mRNA alternative polyadenylation, Mol Cell, 69, 62, 10.1016/j.molcel.2017.11.031 Yang, 2010, Proteasomal activity is required to initiate and to sustain translational activation of messenger RNA encoding the stem-loop-binding protein during meiotic maturation in mice, Biol Reprod, 82, 123, 10.1095/biolreprod.109.076588 Manley, 1996, SR proteins and splicing control, Genes Dev, 10, 1569, 10.1101/gad.10.13.1569 Ruegsegger, 1998, Human pre-mRNA cleavage factor Im is related to spliceosomal SR proteins and can be reconstituted in vitro from recombinant subunits, Mol Cell, 1, 243, 10.1016/S1097-2765(00)80025-8 Gruber, 2012, Cleavage factor Im is a key regulator of 3' UTR length, RNA Biol, 9, 1405, 10.4161/rna.22570 Schafer, 2018, Reconstitution of mammalian cleavage factor II involved in 3' processing of mRNA precursors, RNA, 24, 1721, 10.1261/rna.068056.118 Kamieniarz-Gdula, 2019, Selective roles of vertebrate PCF11 in premature and full-length transcript termination, Mol Cell, 74, 158, 10.1016/j.molcel.2019.01.027 Papasaikas, 2016, The spliceosome: the ultimate RNA chaperone and sculptor, Trends Biochem Sci, 41, 33, 10.1016/j.tibs.2015.11.003 Gunderson, 1998, U1 snRNP inhibits pre-mRNA polyadenylation through a direct interaction between U1 70K and poly(A) polymerase, Mol Cell, 1, 255, 10.1016/S1097-2765(00)80026-X Berg, 2012, U1 snRNP determines mRNA length and regulates isoform expression, Cell, 150, 53, 10.1016/j.cell.2012.05.029 Kaida, 2010, U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation, Nature, 468, 664, 10.1038/nature09479 Kuhn, 2009, Poly(A) tail length is controlled by the nuclear poly(A)-binding protein regulating the interaction between poly(A) polymerase and the cleavage and polyadenylation specificity factor, J Biol Chem, 284, 22803, 10.1074/jbc.M109.018226 Tudek, 2019, Escaping nuclear decay: the significance of mRNA export for gene expression, Curr Genet, 65, 473, 10.1007/s00294-018-0913-x Jenal, 2012, The poly(A)-binding protein nuclear 1 suppresses alternative cleavage and polyadenylation sites, Cell, 149, 538, 10.1016/j.cell.2012.03.022 Sakai, 1995, cDNA sequence and chromosomal localization of a novel human protein, RBQ-1 (RBBP6), that binds to the retinoblastoma gene product, Genomics, 30, 98, 10.1006/geno.1995.0017 Simons, 1997, PACT: cloning and characterization of a cellular p53 binding protein that interacts with Rb, Oncogene, 14, 145, 10.1038/sj.onc.1200825 Di Giammartino, 2014, RBBP6 isoforms regulate the human polyadenylation machinery and modulate expression of mRNAs with AU-rich 3' UTRs, Genes Dev, 28, 2248, 10.1101/gad.245787.114 Cevher, 2010, Connections between 3'-end processing and DNA damage response, Wiley Interdiscipl Rev RNA, 1, 193, 10.1002/wrna.20 Birse, 1998, Coupling termination of transcription to messenger RNA maturation in yeast, Science, 280, 298, 10.1126/science.280.5361.298 Pinto, 2011, RNA polymerase II kinetics in polo polyadenylation signal selection, EMBO J, 30, 2431, 10.1038/emboj.2011.156 de la Mata, 2003, A slow RNA polymerase II affects alternative splicing in vivo, Mol Cell, 12, 525, 10.1016/j.molcel.2003.08.001 Yu, 2016, RNA polymerase II depletion promotes transcription of alternative mRNA species, BMC Mol Biol, 17, 20, 10.1186/s12867-016-0074-8 Oktaba, 2015, ELAV links paused Pol II to alternative polyadenylation in the Drosophila nervous system, Mol Cell, 57, 341, 10.1016/j.molcel.2014.11.024 Chan, 2011, Pre-mRNA 3'-end processing complex assembly and function, Wiley Interdiscipl Rev RNA, 2, 321, 10.1002/wrna.54 Nam, 2014, Global analyses of the effect of different cellular contexts on microRNA targeting, Mol Cell, 53, 1031, 10.1016/j.molcel.2014.02.013 Brumbaugh, 2018, Nudt21 controls cell fate by connecting alternative polyadenylation to chromatin signaling, Cell, 172, 106, 10.1016/j.cell.2017.11.023 Plass, 2017, Highly accessible AU-rich regions in 3' untranslated regions are hotspots for binding of regulatory factors, PLoS Comput Biol, 13, 10.1371/journal.pcbi.1005460 Garneau, 2007, The highways and byways of mRNA decay, Nat Rev Mol Cell Biol, 8, 113, 10.1038/nrm2104 Gupta, 2014, Alternative polyadenylation diversifies post-transcriptional regulation by selective RNA-protein interactions, Mol Syst Biol, 10, 10.1002/msb.135068 Spies, 2013, 3' UTR-isoform choice has limited influence on the stability and translational efficiency of most mRNAs in mouse fibroblasts, Genome Res, 23, 2078, 10.1101/gr.156919.113 Moqtaderi, 2018, Extensive structural differences of closely related 3' mRNA isoforms: links to Pab1 binding and mRNA stability, Mol Cell, 72, 849, 10.1016/j.molcel.2018.08.044 Geisberg, 2014, Global analysis of mRNA isoform half-lives reveals stabilizing and destabilizing elements in yeast, Cell, 156, 812, 10.1016/j.cell.2013.12.026 Tycowski, 2016, Myriad triple-helix-forming structures in the transposable element RNAs of plants and fungi, Cell Rep, 15, 1266, 10.1016/j.celrep.2016.04.010 Lee, 2010, Systematic analysis of cis-elements in unstable mRNAs demonstrates that CUGBP1 is a key regulator of mRNA decay in muscle cells, PLoS One, 5, 10.1371/journal.pone.0011201 O'Neill, 2018, The 3' UTRs of brain-derived neurotrophic factor transcripts differentially regulate the dendritic arbor, Front Cell Neurosci, 12 Oe, 2016, Mechanism of the dendritic translation and localization of brain-derived neurotrophic factor, Cell Struct Funct, 41, 23, 10.1247/csf.15015 Oliveira, 2019, Cell cycle kinase polo is controlled by a widespread 3' untranslated region regulatory sequence in Drosophila melanogaster, Mol Cell Biol, 39, 10.1128/MCB.00581-18 Fu, 2018, Crosstalk between alternative polyadenylation and miRNAs in the regulation of protein translational efficiency, Genome Res, 28, 1656, 10.1101/gr.231506.117 An, 2008, Distinct role of long 3' UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons, Cell, 134, 175, 10.1016/j.cell.2008.05.045 Bertrand, 1998, Localization of ASH1 mRNA particles in living yeast, Mol Cell, 2, 437, 10.1016/S1097-2765(00)80143-4 Niedner, 2014, Of social molecules: the interactive assembly of ASH1 mRNA-transport complexes in yeast, RNA Biol, 11, 998, 10.4161/rna.29946 Ephrussi, 1991, Oskar organizes the germ plasm and directs localization of the posterior determinant nanos, Cell, 66, 37, 10.1016/0092-8674(91)90137-N Neve, 2016, Subcellular RNA profiling links splicing and nuclear DICER1 to alternative cleavage and polyadenylation, Genome Res, 26, 24, 10.1101/gr.193995.115 Chen, 2009, Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: functional role of a nuclear noncoding RNA, Mol Cell, 35, 467, 10.1016/j.molcel.2009.06.027 Loya, 2008, The 3'-UTR mediates the cellular localization of an mRNA encoding a short plasma membrane protein, RNA, 14, 1352, 10.1261/rna.867208 Reid, 2015, Diversity and selectivity in mRNA translation on the endoplasmic reticulum, Nat Rev Mol Cell Biol, 16, 221, 10.1038/nrm3958 Taliaferro, 2016, RNA sequence context effects measured in vitro predict in vivo protein binding and regulation, Mol Cell, 64, 294, 10.1016/j.molcel.2016.08.035 Jambhekar, 2007, Cis-acting determinants of asymmetric, cytoplasmic RNA transport, RNA, 13, 625, 10.1261/rna.262607 Yudin, 2008, Localized regulation of axonal RanGTPase controls retrograde injury signaling in peripheral nerve, Neuron, 59, 241, 10.1016/j.neuron.2008.05.029 Andreassi, 2009, To localize or not to localize: mRNA fate is in 3'UTR ends, Trends Cell Biol, 19, 465, 10.1016/j.tcb.2009.06.001 Ciolli Mattioli, 2019, Alternative 3' UTRs direct localization of functionally diverse protein isoforms in neuronal compartments, Nucleic Acids Res, 47, 2560, 10.1093/nar/gky1270 Ma, 2018, A membraneless organelle associated with the endoplasmic reticulum enables 3'UTR-mediated protein-protein interactions, Cell, 175, 1492, 10.1016/j.cell.2018.10.007 Curinha, 2014, Implications of polyadenylation in health and disease, Nucleus, 5, 508, 10.4161/nucl.36360 Chang, 2017, Alternative polyadenylation in human diseases, Endocrinol Metabol, 32, 413, 10.3803/EnM.2017.32.4.413 Lin, 2012, An in-depth map of polyadenylation sites in cancer, Nucleic Acids Res, 40, 8460, 10.1093/nar/gks637 Lin, 2012, Activity-dependent alternative splicing increases persistent sodium current and promotes seizure, J Neurosci, 32, 7267, 10.1523/JNEUROSCI.6042-11.2012 Masamha, 2018, The contribution of alternative polyadenylation to the cancer phenotype, Carcinogenesis, 39, 2, 10.1093/carcin/bgx096 Xue, 2018, Recurrent tumor-specific regulation of alternative polyadenylation of cancer-related genes, BMC Genomics, 19, 10.1186/s12864-018-4903-7 Wang, 2016, The 3'UTR signature defines a highly metastatic subgroup of triple-negative breast cancer, Oncotarget, 7, 59834, 10.18632/oncotarget.10975 Wang, 2019, Integrative 3' untranslated region-based model to identify patients with low risk of axillary lymph node metastasis in operable triple-negative breast cancer, The Oncologist, 24, 22, 10.1634/theoncologist.2017-0609 Park, 2018, 3' UTR shortening represses tumor-suppressor genes in trans by disrupting ceRNA crosstalk, Nat Genet, 50, 783, 10.1038/s41588-018-0118-8 Sun, 2017, NUDT21 regulates 3'-UTR length and microRNA-mediated gene silencing in hepatocellular carcinoma, Cancer Lett, 410, 158, 10.1016/j.canlet.2017.09.026 Zhu, 2016, MicroRNA-181a promotes proliferation and inhibits apoptosis by suppressing CFIm25 in osteosarcoma, Mol Med Rep, 14, 4271, 10.3892/mmr.2016.5741 Tan, 2018, NUDT21 negatively regulates PSMB2 and CXXC5 by alternative polyadenylation and contributes to hepatocellular carcinoma suppression, Oncogene, 37, 4887, 10.1038/s41388-018-0280-6 Ogorodnikov, 2018, Transcriptome 3'end organization by PCF11 links alternative polyadenylation to formation and neuronal differentiation of neuroblastoma, Nat Commun, 9, 10.1038/s41467-018-07580-5 Wang, 2019, Regulation of intronic polyadenylation by PCF11 impacts mRNA expression of long genes, Cell Rep, 26, 2766, 10.1016/j.celrep.2019.02.049 Fischl, 2019, hnRNPC regulates cancer-specific alternative cleavage and polyadenylation profiles, Nucleic Acids Res, 47, 7580, 10.1093/nar/gkz461 Lianoglou, 2013, Ubiquitously transcribed genes use alternative polyadenylation to achieve tissue-specific expression, Genes Dev, 27, 2380, 10.1101/gad.229328.113 Zheng, 2016, 3'READS+, a sensitive and accurate method for 3' end sequencing of polyadenylated RNA, RNA, 22, 1631, 10.1261/rna.057075.116 Hoque, 2014, Accurate mapping of cleavage and polyadenylation sites by 3' region extraction and deep sequencing, Methods Mol Biol, 1125, 119, 10.1007/978-1-62703-971-0_10 Routh, 2017, Poly(A)-ClickSeq: click-chemistry for next-generation 3-end sequencing without RNA enrichment or fragmentation, Nucleic Acids Res, 45, 10.1093/nar/gkx286 Wang, 2015, Profiling of alternative polyadenylation sites in luminal B breast cancer using the SAPAS method, Int J Mol Med, 35, 39, 10.3892/ijmm.2014.1973 Ha, 2018, QAPA: a new method for the systematic analysis of alternative polyadenylation from RNA-seq data, Genome Biol, 19, 10.1186/s13059-018-1414-4 Bray, 2016, Near-optimal probabilistic RNA-seq quantification, Nat Biotechnol, 34, 525, 10.1038/nbt.3519 Ye, 2018, APAtrap: identification and quantification of alternative polyadenylation sites from RNA-seq data, Bioinformatics, 34, 1841, 10.1093/bioinformatics/bty029 Chang, 2018, An integrative model for alternative polyadenylation, IntMAP, delineates mTOR-modulated endoplasmic reticulum stress response, Nucleic Acids Res, 46, 5996, 10.1093/nar/gky340 Arefeen, 2018, TAPAS: tool for alternative polyadenylation site analysis, Bioinformatics, 34, 2521, 10.1093/bioinformatics/bty110 Van Etten, 2017, Targeting a single alternative polyadenylation site coordinately blocks expression of androgen receptor mRNA splice variants in prostate cancer, Cancer Res, 77, 5228, 10.1158/0008-5472.CAN-17-0320