BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Analyses of alternative polyadenylation: from old school biochemistry to high-throughput technologies

  • Yeh, Hsin-Sung (Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota) ;
  • Zhang, Wei (Department of Computer Science and Engineering, University of Minnesota) ;
  • Yong, Jeongsik (Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota)
  • Received : 2017.01.31
  • Published : 2017.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Alternations in usage of polyadenylation sites during transcription termination yield transcript isoforms from a gene. Recent findings of transcriptome-wide alternative polyadenylation (APA) as a molecular response to changes in biology position APA not only as a molecular event of early transcriptional termination but also as a cellular regulatory step affecting various biological pathways. With the development of high-throughput profiling technologies at a single nucleotide level and their applications targeted to the 3'-end of mRNAs, dynamics in the landscape of mRNA 3'-end is measureable at a global scale. In this review, methods and technologies that have been adopted to study APA events are discussed. In addition, various bioinformatics algorithms for APA isoform analysis using publicly available RNA-seq datasets are introduced.

Keywords

References

  1. Proudfoot NJ (2011) Ending the message: poly(A) signals then and now. Genes Dev 25, 1770-1782 https://doi.org/10.1101/gad.17268411
  2. Colgan DF and Manley JL (1997) Mechanism and regulation of mRNA polyadenylation. Genes Dev 11, 2755-2766 https://doi.org/10.1101/gad.11.21.2755
  3. Zhang X, Virtanen A and Kleiman FE (2010) To polyadenylate or to deadenylate: That is the question. Cell Cycle 9, 4437-4449 https://doi.org/10.4161/cc.9.22.13887
  4. Danckwardt S, Kaufmann I, Gentzel M et al (2007) Splicing factors stimulate polyadenylation via USEs at noncanonical 3' end formation signals. EMBO J 26, 2658-2669 https://doi.org/10.1038/sj.emboj.7601699
  5. Graber JH, Cantor CR, Mohr SC and Smith TF (1999) Genomic detection of new yeast pre-mRNA 3'-endprocessing signals. Nucleic Acids Res 27, 888-894 https://doi.org/10.1093/nar/27.3.888
  6. Beaudoing E, Freier S, Wyatt JR, Claverie JM and Gautheret D (2000) Patterns of Variant Polyadenylation Signal Usage in Human Genes. Genome Res 10, 1001-1010 https://doi.org/10.1101/gr.10.7.1001
  7. Derti A, Garrett-Engele P, MacIsaac KD et al (2012) A quantitative atlas of polyadenylation in five mammals. Genome Res 22, 1173-1183 https://doi.org/10.1101/gr.132563.111
  8. Tian B and Manley JL (2013) Alternative cleavage and polyadenylation: the long and short of it. Trends Biochem Sci 38, 312-320 https://doi.org/10.1016/j.tibs.2013.03.005
  9. Fabian MR, Sonenberg N and Filipowicz W (2010) Regulation of mRNA Translation and Stability by microRNAs. Annu Rev Biochem 79, 351-379 https://doi.org/10.1146/annurev-biochem-060308-103103
  10. Yeh HS and Yong J (2016) Alternative Polyadenylation of mRNAs: 3'-Untranslated Region Matters in Gene Expression. Mol Cells 39, 281-285 https://doi.org/10.14348/molcells.2016.0035
  11. Chang J, Zhang W, Yeh H et al (2015) mRNA 3prime]-UTR shortening is a molecular signature of mTORC1 activation. Nat Commun 6, 7218 https://doi.org/10.1038/ncomms8218
  12. Hoque M, Ji Z, Zheng D et al (2013) Analysis of alternative cleavage and polyadenylation by 3prime] region extraction and deep sequencing. Nat Methods 10, 133-139 https://doi.org/10.1038/nmeth.2288
  13. Sandberg R, Neilson JR, Sarma A, Sharp PA and Burge CB (2008) Proliferating Cells Express mRNAs with Shortened 3' Untranslated Regions and Fewer MicroRNA Target Sites. Science 320, 1643-1647 https://doi.org/10.1126/science.1155390
  14. Sandberg R, Neilson JR, Sarma A, Sharp PA and Burge CB (2008) Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites. Science 320, 1643-1647 https://doi.org/10.1126/science.1155390
  15. Ulitsky I, Shkumatava A, Jan CH et al (2012) Extensive alternative polyadenylation during zebrafish development. Genome Res 22, 2054-2066 https://doi.org/10.1101/gr.139733.112
  16. Zhang H, Lee JY and Tian B (2005) Biased alternative polyadenylation in human tissues. Genome Biol 6, R100 https://doi.org/10.1186/gb-2005-6-12-r100
  17. Mayr C and Bartel DP (2009) Widespread Shortening of 3'UTRs by Alternative Cleavage and Polyadenylation Activates Oncogenes in Cancer Cells. Cell 138, 673-684 https://doi.org/10.1016/j.cell.2009.06.016
  18. Singh P, Alley TL, Wright SM et al (2009) Global Changes in Processing of mRNA 3' Untranslated Regions Characterize Clinically Distinct Cancer Subtypes. Cancer Res 69, 9422-9430 https://doi.org/10.1158/0008-5472.CAN-09-2236
  19. Morris AR, Bos A, Diosdado B et al (2012) Alternative Cleavage and Polyadenylation during Colorectal Cancer Development. Clin Cancer Res 18, 5256-5266 https://doi.org/10.1158/1078-0432.CCR-12-0543
  20. Lembo A, Di Cunto F and Provero P (2012) Shortening of 3-UTRs Correlates with Poor Prognosis in Breast and Lung Cancer. PLoS One 7, e31129 https://doi.org/10.1371/journal.pone.0031129
  21. Setzer DR, McGrogan M, Nunberg JH and Schimke RT (1980) Size heterogeneity in the 3' end of dihydrofolate reductase messenger RNAs in mouse cells. Cell 22, 361-370 https://doi.org/10.1016/0092-8674(80)90346-3
  22. Alt FW, Bothwell ALM, Knapp M et al (1980) Synthesis of secreted and membrane-bound immunoglobulin mu heavy chains is directed by mRNAs that differ at their 3' ends. Cell 20, 293-301 https://doi.org/10.1016/0092-8674(80)90615-7
  23. Early P, Rogers J, Davis M et al (1980) Two mRNAs can be produced from a single immunoglobulin $\mu$ gene by alternative RNA processing pathways. Cell 20, 313-319 https://doi.org/10.1016/0092-8674(80)90617-0
  24. Rogers J, Early P, Carter C et al (1980) Two mRNAs with different 3' ends encode membrane-bound and secreted forms of immunoglobulin $\mu$ chain. Cell 20, 303-312 https://doi.org/10.1016/0092-8674(80)90616-9
  25. Tian B, Hu J, Zhang H and Lutz CS (2005) A large-scale analysis of mRNA polyadenylation of human and mouse genes. Nucleic Acids Res 33, 201-212 https://doi.org/10.1093/nar/gki158
  26. Yan J and Marr TG (2005) Computational analysis of 3'-ends of ESTs shows four classes of alternative polyadenylation in human, mouse, and rat. Genome Res 15, 369-375 https://doi.org/10.1101/gr.3109605
  27. Ji Z and 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, e8419 https://doi.org/10.1371/journal.pone.0008419
  28. Flavell SW, Kim TK, Gray JM et al (2008) Genome-Wide Analysis of MEF2 Transcriptional Program Reveals Synaptic Target Genes and Neuronal Activity-Dependent Polyadenylation Site Selection. Neuron 60, 1022-1038 https://doi.org/10.1016/j.neuron.2008.11.029
  29. Shi Y (2012) Alternative polyadenylation: New insights from global analyses. RNA 18, 2105-2117 https://doi.org/10.1261/rna.035899.112
  30. Nagalakshmi U, Wang Z, Waern K et al (2008) The Transcriptional Landscape of the Yeast Genome Defined by RNA Sequencing. Science 320, 1344-1349 https://doi.org/10.1126/science.1158441
  31. Wang ET, Sandberg R, Luo S et al (2008) Alternative isoform regulation in human tissue transcriptomes. Nature 456, 470-476 https://doi.org/10.1038/nature07509
  32. Ozsolak F and Milos PM (2011) RNA sequencing: advances, challenges and opportunities. Nat Rev Genet 12, 87-98 https://doi.org/10.1038/nrg2934
  33. Bray NL, Pimentel H, Melsted P and Pachter L (2016) Near-optimal probabilistic RNA-seq quantification. Nat Biotechnol 34, 525-527 https://doi.org/10.1038/nbt.3519
  34. Xia Z, Donehower LA, Cooper TA et al (2014) Dynamic analyses of alternative polyadenylation from RNA-seq reveal a 3'-UTR landscape across seven tumour types. Nat Commun 5, 5274 https://doi.org/10.1038/ncomms6274
  35. Wang W, Wei Z and Li H (2014) A change-point model for identifying 3'UTR switching by next-generation RNA sequencing. Bioinformatics 30, 2162-2170 https://doi.org/10.1093/bioinformatics/btu189
  36. Grassi E, Mariella E, Lembo A, Molineris I and Provero P (2016) Roar: detecting alternative polyadenylation with standard mRNA sequencing libraries. BMC Bioinformatics 17, 423 https://doi.org/10.1186/s12859-016-1254-8
  37. Le Pera L, Mazzapioda M and Tramontano A (2015) 3USS: a web server for detecting alternative 3'UTRs from RNA-seq experiments. Bioinformatics 31, 1845-1847 https://doi.org/10.1093/bioinformatics/btv035
  38. Shenker S, Miura P, Sanfilippo P and Lai EC (2015) IsoSCM: improved and alternative 3' UTR annotation using multiple change-point inference. RNA 21, 14-27 https://doi.org/10.1261/rna.046037.114
  39. Birol I, Raymond A, Chiu R et al (2015) Kleat: cleavage site analysis of transcriptomes. Pac Symp Biocomput 2015, 347-358
  40. Kim M, You B and Nam JW (2015) Global estimation of the 3' untranslated region landscape using RNA sequencing. Methods 83, 111-117 https://doi.org/10.1016/j.ymeth.2015.04.011
  41. Mangone M, Manoharan AP, Thierry-Mieg D et al (2010) The Landscape of C. elegans 3'UTRs. Science 329, 432-435 https://doi.org/10.1126/science.1191244
  42. Fox-Walsh K, Davis-Turak J, Zhou Y, Li H and Fu XD (2011) A Multiplex RNA-seq Strategy to Profile Poly(A(+)) RNA: Application to Analysis of Transcription Response and 3' End Formation. Genomics 98, 266-271 https://doi.org/10.1016/j.ygeno.2011.04.003
  43. Shepard PJ, Choi EA, Lu J, Flanagan LA, Hertel KJ and Shi Y (2011) Complex and dynamic landscape of RNA polyadenylation revealed by PAS-Seq. RNA 17, 761-772 https://doi.org/10.1261/rna.2581711
  44. Martin G, Gruber AR, Keller W and Zavolan M (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, 753-763 https://doi.org/10.1016/j.celrep.2012.05.003
  45. Beck AH, Weng Z, Witten DM et al (2010) 3'-end sequencing for expression quantification (3SEQ) from archival tumor samples. PLoS One 5, e8768 https://doi.org/10.1371/journal.pone.0008768
  46. Fu Y, Sun Y, Li Y et al (2011) Differential genome-wide profiling of tandem 3' UTRs among human breast cancer and normal cells by high-throughput sequencing. Genome Res 21, 741-747 https://doi.org/10.1101/gr.115295.110
  47. Ozsolak F, Platt AR, Jones DR et al (2009) Direct RNA sequencing. Nature 461, 814-818 https://doi.org/10.1038/nature08390
  48. Jan CH, Friedman RC, Ruby JG and Bartel DP (2011) Formation, regulation and evolution of Caenorhabditis elegans 3'UTRs. Nature 469, 97-101 https://doi.org/10.1038/nature09616
  49. Hafner M, Renwick N, Brown M et al (2011) RNA-ligasedependent biases in miRNA representation in deepsequenced small RNA cDNA libraries. RNA 17, 1697-1712 https://doi.org/10.1261/rna.2799511
  50. Steijger T, Abril JF, Engstrom PG et al (2013) Assessment of transcript reconstruction methods for RNA-seq. Nat Meth 10, 1177-1184 https://doi.org/10.1038/nmeth.2714
  51. Rhoads A and Au KF (2015) PacBio Sequencing and Its Applications. Genomics Proteomics Bioinformatics 13, 278-289 https://doi.org/10.1016/j.gpb.2015.08.002
  52. Sharon D, Tilgner H, Grubert F and Snyder M (2013) A single-molecule long-read survey of the human transcriptome. Nat Biotechnol 31, 1009-1014 https://doi.org/10.1038/nbt.2705
  53. O'Grady T, Wang X, Honer Zu Bentrup K, Baddoo M, Concha M and Flemington EK (2016) Global transcript structure resolution of high gene density genomes through multi-platform data integration. Nucleic Acids Res 44, e145 https://doi.org/10.1093/nar/gkw629
  54. Chen L, Kostadima M, Martens JH et al (2014) Transcriptional diversity during lineage commitment of human blood progenitors. Science 345, 1251033 https://doi.org/10.1126/science.1251033
  55. Singh N, Sahu DK, Chowdhry R et al (2015) IsoSeq analysis and functional annotation of the infratentorial ependymoma tumor tissue on PacBio RSII platform. Meta Gene 7, 70-75
  56. Abdel-Ghany S, Hamilton M, Jacobi JL et al (2016) A survey of the sorghum transcriptome using single-molecule long reads. Nature Commun 7, 11706 https://doi.org/10.1038/ncomms11706
  57. Au KF, Underwood JG, Lee L and Wong WH (2012) Improving PacBio Long Read Accuracy by Short Read Alignment. PLoS One 7, e46679 https://doi.org/10.1371/journal.pone.0046679
  58. Au KF, Sebastiano V, Afshar PT et al (2013) Characterization of the human ESC transcriptome by hybrid sequencing. Proc Natl Acad Sci U S A 110, E4821-E4830 https://doi.org/10.1073/pnas.1320101110
  59. Sandberg R, Neilson JR, Sarma A, Sharp PA and Burge CB (2008) Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites. Science 320, 1643-1647 https://doi.org/10.1126/science.1155390
  60. Graham RR, Kyogoku C, Sigurdsson S et al (2007) Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus. Proc Natl Acad Sci U S A 104, 6758-6763 https://doi.org/10.1073/pnas.0701266104
  61. Weirather JL, Afshar PT, Clark TA et al (2015) Characterization of fusion genes and the significantly expressed fusion isoforms in breast cancer by hybrid sequencing. Nucleic Acids Res 43, e116 https://doi.org/10.1093/nar/gkv562
  62. Trapnell C, Williams BA, Pertea G et al (2010) Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol 28, 511-515 https://doi.org/10.1038/nbt.1621