Tunable protein synthesis by transcript isoforms in human cells

eLife

Volumn 5, Issue JANUARY2016, 2016, Pages

  Floor, Stephen N ^a   Doudna, Jennifer A ^a,b,c,d  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b University of California   (United States)

^c LAWRENCE BERKELEY NATIONAL LABORATORY   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL LINE; CONTROLLED STUDY; DNA TRANSCRIPTION; EUKARYOTE; GENE EXPRESSION; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; POLYADENYLATION; POLYSOME; PROTEIN SYNTHESIS; RNA SPLICING; UNTRANSLATED REGION; ALTERNATIVE RNA SPLICING; BIOSYNTHESIS; EPITHELIUM CELL; GENE EXPRESSION REGULATION; METABOLISM;

ISOPROTEIN; MESSENGER RNA;

ALTERNATIVE SPLICING; CELL LINE; EPITHELIAL CELLS; GENE EXPRESSION REGULATION; HUMANS; POLYRIBOSOMES; PROTEIN BIOSYNTHESIS; PROTEIN ISOFORMS; RNA, MESSENGER;

EID: 84958567960     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/elife.10921     Document Type: Article

References (111)

1. Amrani N, Ghosh S, Mangus DA, Jacobson A. 2008. Translation factors promote the formation of two states of the closed-loop mRNP. Nature 453: 1276-1280. doi: 10. 1038/nature06974.
2. Arava Y, Wang Y, Storey JD, Liu CL, Brown PO, Herschlag D. 2003. Genome-wide analysis of mRNA translation profiles in saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 100: 3889-3894. doi: 10. 1073/pnas. 0635171100.
3. Arribere JA, Gilbert WV. 2013. Roles for transcript leaders in translation and mRNA decay revealed by transcript leader sequencing. Genome Research 23: 977-987. doi: 10. 1101/gr. 150342. 112.
4. Barbosa-Morais NL, Irimia M, Pan Q, Xiong HY, Gueroussov S, Lee LJ, Slobodeniuc V, Kutter C, Watt S, Colak R, Kim T, Misquitta-Ali CM, Wilson MD, Kim PM, Odom DT, Frey BJ, Blencowe BJ. 2012. The evolutionary landscape of alternative splicing in vertebrate species. Science 338: 1587-1593. doi: 10. 1126/science. 1230612.
5. Bartel DP. 2009. MicroRNAs: target recognition and regulatory functions. Cell 136: 215-233. doi: 10. 1016/j. cell. 2009. 01. 002.
6. Bates JG, Salzman J, May D, Garcia PB, Hogan GJ, McIntosh M, Schlissel MS, Brown PO. 2012. Extensive gene-specific translational reprogramming in a model of b cell differentiation and abl-dependent transformation. PloS One 7: e37108. doi: 10. 1371/journal. pone. 0037108.
7. Berkovits BD, Mayr C. 2015. Alternative 3' UTRs act as scaffolds to regulate membrane protein localization. Nature 522. doi: 10. 1038/nature14321.
8. Besse F, Ephrussi A. 2008. Translational control of localized mRNAs: restricting protein synthesis in space and time. Nature Reviews Molecular Cell Biology 9: 971-980. doi: 10. 1038/nrm2548.
9. Boutz PL, Bhutkar A, Sharp PA. 2015. Detained introns are a novel, widespread class of post-transcriptionally spliced introns. Genes & Development 29: 63-80. doi: 10. 1101/gad. 247361. 114.
10. Brar GA, Yassour M, Friedman N, Regev A, Ingolia NT, Weissman JS. 2012. High-resolution view of the yeast meiotic program revealed by ribosome profiling. Science 335: 552-557. doi: 10. 1126/science. 1215110.
11. Brooks SA, Blackshear PJ. 2013. Tristetraprolin (tTP): interactions with mRNA and proteins, and current thoughts on mechanisms of action. Biochimica Et Biophysica Acta (BBA)-Gene Regulatory Mechanisms 1829: 666-679. doi: 10. 1016/j. bbagrm. 2013. 02. 003.
12. Calvo SE, Pagliarini DJ, Mootha VK. 2009. Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans. Proceedings of the National Academy of Sciences of the United States of America 106: 7507-7512. doi: 10. 1073/pnas. 0810916106.
13. Chuang RY, Weaver PL, Liu Z, Chang TH. 1997. Requirement of the DEAD-box protein Ded1p for messenger RNA translation. Science 275: 1468-1471. doi: 10. 1126/science. 275. 5305. 1468.
14. Cliff N. 1993. Dominance statistics: ordinal analyses to answer ordinal questions. Psychological Bulletin 114: 494-509. doi: 10. 1037/0033-2909. 114. 3. 494.
15. Costello J, Castelli LM, Rowe W, Kershaw CJ, Talavera D, Mohammad-Qureshi SS, Sims PF, Grant CM, Pavitt GD, Hubbard SJ, Ashe MP. 2015. Global mRNA selection mechanisms for translation initiation. Genome Biology 16: 10. doi: 10. 1186/s13059-014-0559-z.
16. Darnell JC, Van Driesche SJ, Zhang C, Hung KY, Mele A, Fraser CE, Stone EF, Chen C, Fak JJ, Chi SW, Licatalosi DD, Richter JD, Darnell RB. 2011. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146: 247-261. doi: 10. 1016/j. cell. 2011. 06. 013.
17. de Klerk E, 't Hoen PA. 2015. Alternative mRNA transcription, processing, and translation: insights from RNA sequencing. Trends in Genetics: TIG 31: 128-139. doi: 10. 1016/j. tig. 2015. 01. 001.
18. Ender C, Krek A, Friedlä nder MR, Beitzinger M, Weinmann L, Chen W, Pfeffer S, Rajewsky N, Meister G. 2008. A human snoRNA with microRNA-like functions. Molecular Cell 32: 519-528. doi: 10. 1016/j. molcel. 2008. 10. 017.
19. Ferreira JP, Overton KW, Wang CL. 2013. Tuning gene expression with synthetic upstream open reading frames. Proceedings of the National Academy of Sciences of the United States of America 110: 11284-11289. doi: 10. 1073/pnas. 1305590110.
20. Fischer BE, Wasbrough E, Meadows LA, Randlet O, Dorus S, Karr TL, Russell S. 2012. Conserved properties of drosophila and human spermatozoal mRNA repertoires. Proceedings Biological Sciences/the Royal Society 279: 2636-2644. doi: 10. 1098/rspb. 2012. 0153.
21. Folco EG, Lei H, Hsu JL, Reed R. 2012. Small-scale nuclear extracts for functional assays of gene-expression machineries. Journal of Visualized Experiments 64: e4140. doi: 10. 3791/4140.
22. Fukaya T, Tomari Y. 2011. PABP is not essential for microRNA-mediated translational repression and deadenylation in vitro. The EMBO Journal 30: 4998-5009. doi: 10. 1038/emboj. 2011. 426.
23. Galili T. 2015. Dendextend: an r package for visualizing, adjusting and comparing trees of hierarchical clustering. Bioinformatics 31: 3718-3720. doi: 10. 1093/bioinformatics/btv428.
24. Garcia DM, Baek D, Shin C, Bell GW, Grimson A, Bartel DP. 2011. Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs. Nature Structural & Molecular Biology 18: 1139-1146. doi: 10. 1038/nsmb. 2115.
25. Geiger T, Wehner A, Schaab C, Cox J, Mann M. 2012. Comparative proteomic analysis of eleven common cell lines reveals ubiquitous but varying expression of most proteins. Molecular & Cellular Proteomics 11: M111. 014050. M111014050. doi: 10. 1074/mcp. M111. 014050.
26. Ghazalpour A, Bennett B, Petyuk VA, Orozco L, Hagopian R, Mungrue IN, Farber CR, Sinsheimer J, Kang HM, Furlotte N, Park CC, Wen PZ, Brewer H, Weitz K, Camp DG, Pan C, Yordanova R, Neuhaus I, Tilford C, Siemers N, Gargalovic P, Eskin E, Kirchgessner T, Smith DJ, Smith RD, Lusis AJ. 2011. Comparative analysis of proteome and transcriptome variation in mouse. PLoS Genetics 7: e1001393. doi: 10. 1371/journal. pgen. 1001393.
27. Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA, Smith HO. 2009. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nature Methods 6: 343-345. doi: 10. 1038/nmeth. 1318.
28. Godchaux W, Adamson SD, Herbert E. 1967. Effects of cycloheximide on polyribosome function in reticulocytes. Journal of Molecular Biology 27: 57-72. doi: 10. 1016/0022-2836(67)90351-8.
29. Grant CM, Miller PF, Hinnebusch AG. 1994. Requirements for intercistronic distance and level of eukaryotic initiation factor 2 activity in reinitiation on GCN4 mRNA vary with the downstream cistron. Molecular and Cellular Biology 14: 2616-2628. doi: 10. 1128/MCB. 14. 4. 2616.
30. Gray NK, Hentze MW. 1994. Iron regulatory protein prevents binding of the 43S translation pre-initiation complex to ferritin and eALAS mRNAs. The EMBO Journal 13: 3882-3891.
31. Gö hring J, Jacak J, Barta A. 2014. Imaging of endogenous messenger RNA splice variants in living cells reveals nuclear retention of transcripts inaccessible to nonsense-mediated decay in arabidopsis. The Plant Cell 26: 754-764. doi: 10. 1105/tpc. 113. 118075.
32. Han K, Jaimovich A, Dey G, Ruggero D, Meyuhas O, Sonenberg N, Meyer T. 2014. Parallel measurement of dynamic changes in translation rates in single cells. Nature Methods 11: 86-93. doi: 10. 1038/nmeth. 2729.
33. Harding HP, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, Ron D. 2000. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Molecular Cell 6: 1099-1108. doi: 10. 1016/S1097-2765(00)00108-8.
34. Hinnebusch AG, Lorsch JR. 2012. The mechanism of eukaryotic translation initiation: new insights and challenges. Cold Spring Harbor Perspectives in Biology 4. doi: 10. 1101/cshperspect. a011544.
35. Hinnebusch AG. 2005. Translational regulation of GCN4 and the general amino acid control of yeast. Annual Review of Microbiology 59: 407-450. doi: 10. 1146/annurev. micro. 59. 031805. 133833.
36. Ingolia NT, Brar GA, Stern-Ginossar N, Harris MS, Talhouarne GJ, Jackson SE, Wills MR, Weissman JS. 2014. Ribosome profiling reveals pervasive translation outside of annotated protein-coding genes. Cell Reports 8: 1365-1379. doi: 10. 1016/j. celrep. 2014. 07. 045.
37. Ingolia NT, Ghaemmaghami S, Newman JR, Weissman JS. 2009. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324: 218-223. doi: 10. 1126/science. 1168978.
38. Ingolia NT, Lareau LF, Weissman JS. 2011. Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell 147: 789-802. doi: 10. 1016/j. cell. 2011. 10. 002.
39. Ingolia NT. 2014. Ribosome profiling: new views of translation, from single codons to genome scale. Nature Reviews Genetics 15: 205-213. from. doi: 10. 1038/nrg3645.
40. Ishimura R, Nagy G, Dotu I, Zhou H, Yang XL, Schimmel P, Senju S, Nishimura Y, Chuang JH, Ackerman SL. 2014. RNA function. ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration. Science (New York, N. Y.) 345: 455-459. doi: 10. 1126/science. 1249749.
41. Jangi M, Boutz PL, Paul P, Sharp PA. 2014. Rbfox2 controls autoregulation in RNA-binding protein networks. Genes & Development 28: 637-651. doi: 10. 1101/gad. 235770. 113.
42. Jiao X, Sherman BT, Huang da W, Stephens R, Baseler MW, Lane HC, Lempicki RA. 2012. DAVID-WS: a stateful web service to facilitate gene/protein list analysis. Bioinformatics 28: 1805-1806. doi: 10. 1093/bioinformatics/bts251.
43. Jovanovic M, Rooney MS, Mertins P, Przybylski D, Chevrier N, Satija R, Rodriguez EH, Fields AP, Schwartz S, Raychowdhury R, Mumbach MR, Eisenhaure T, Rabani M, Gennert D, Lu D, Delorey T, Weissman JS, Carr SA, Hacohen N, Regev A. 2015. Immunogenetics. dynamic profiling of the protein life cycle in response to pathogens. Science 347: 1259038. doi: 10. 1126/science. 1259038.
44. Jung H, Gkogkas CG, Sonenberg N, Holt CE. 2014. Remote control of gene function by local translation. Cell 157: 26-40. doi: 10. 1016/j. cell. 2014. 03. 005.
45. Kole R, Krainer AR, Altman S. 2012. RNA therapeutics: beyond RNA interference and antisense oligonucleotides. Nature Reviews. Drug Discovery 11: 125-140. doi: 10. 1038/nrd3625.
46. Kormann MS, Hasenpusch G, Aneja MK, Nica G, Flemmer AW, Herber-Jonat S, Huppmann M, Mays LE, Illenyi M, Schams A, Griese M, Bittmann I, Handgretinger R, Hartl D, Rosenecker J, Rudolph C. 2011. Expression of therapeutic proteins after delivery of chemically modified mRNA in mice. Nature Biotechnology 29: 154-157. doi: 10. 1038/nbt. 1733.
47. Kulak NA, Pichler G, Paron I, Nagaraj N, Mann M. 2014. Minimal, encapsulated proteomic-sample processing applied to copy-number estimation in eukaryotic cells. Nature Methods 11: 319-324. doi: 10. 1038/nmeth. 2834.
48. Lai MC, Chang WC, Shieh SY, Tarn WY. 2010. DDX3 regulates cell growth through translational control of cyclin E1. Molecular and Cellular Biology 30: 5444-5453. doi: 10. 1128/MCB. 00560-10.
49. Langmead B, Salzberg SL. 2012. Fast gapped-read alignment with bowtie 2. Nature Methods 9: 357-359. doi: 10. 1038/nmeth. 1923.
50. Lareau LF, Brooks AN, Soergel DAW, Meng Q, Brenner SE. 2007. The coupling of alternative splicing and nonsense-mediated mRNA decay. Advances in Experimental Medicine and Biology 623: 190-211. doi: 10. 1007/978-0-387-77374-2_12.
51. Londin ER, Hatzimichael E, Loher P, Edelstein L, Shaw C, Delgrosso K, Fortina P, Bray PF, McKenzie SE, Rigoutsos I. 2014. The human platelet: strong transcriptome correlations among individuals associate weakly with the platelet proteome. Biology Direct 9: 3. doi: 10. 1186/1745-6150-9-3.
52. Lorenz R, Bernhart SH, Hö ner zu Siederdissen C, Tafer H, Flamm C, Stadler PF, Hofacker IL. 2011. ViennaRNA package 2. 0. Algorithms for Molecular Biology 6: 26. doi: 10. 1186/1748-7188-6-26.
53. Love MI, Huber W, Anders S. 2014. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology 15: 550. doi: 10. 1186/s13059-014-0550-8.
54. Luo Z, Pan Y, Jeong LS, Liu J, Jia L. 2012. Inactivation of the cullin (cUL)-RING E3 ligase by the NEDD8-activating enzyme inhibitor MLN4924 triggers protective autophagy in cancer cells. Autophagy 8: 1677-1679. doi: 10. 4161/auto. 21484.
55. Maroney PA, Yu Y, Fisher J, Nilsen TW. 2006. Evidence that microRNAs are associated with translating messenger RNAs in human cells. Nature Structural & Molecular Biology 13: 1102-1107. doi: 10. 1038/nsmb1174.
56. Martin M. 2011. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet. journal 17: 10. doi: 10. 14806/ej. 17. 1. 200.
57. Maslon MM, Heras SR, Bellora N, Eyras E, Cá ceres JF. 2014. The translational landscape of the splicing factor SRSF1 and its role in mitosis. eLife 3. e02028. doi. doi: 10. 7554/eLife. 02028.
58. Mayr C, Bartel DP. 2009. Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell 138: 673-684. doi: 10. 1016/j. cell. 2009. 06. 016.
59. Melé M, Ferreira PG, Reverter F, DeLuca DS, Monlong J, Sammeth M, Young TR, Goldmann JM, Pervouchine DD, Sullivan TJ, Johnson R, Segrè AV, Djebali S, Niarchou A, Wright FA, Lappalainen T, Calvo M, Getz G, Dermitzakis ET, Ardlie KG, Guigó R. GTEx Consortium. 2015. Human genomics. the human transcriptome across tissues and individuals. Science 348: 660-665. doi: 10. 1126/science. aaa0355.
60. Merkin J, Russell C, Chen P, Burge CB. 2012. Evolutionary dynamics of gene and isoform regulation in mammalian tissues. Science 338: 1593-1599. doi: 10. 1126/science. 1228186.
61. Merritt C, Rasoloson D, Ko D, Seydoux G. 2008. 3¢ UTRs are the primary regulators of gene expression in the C. elegans germline. Current Biology 18: 1476-1482. doi: 10. 1016/j. cub. 2008. 08. 013.
62. Moore AE, Chenette DM, Larkin LC, Schneider RJ. 2014. Physiological networks and disease functions of RNA-binding protein AUF1. Wiley Interdisciplinary Reviews: RNA 5: 549-564. doi: 10. 1002/wrna. 1230.
63. Müllner D. 2013. fastcluster: fast hierarchical, agglomerative clustering routines for r and python. Journal of Statistical Software 53. doi: 10. 18637/jss. v053. i09.
64. Nott A, Le Hir H, Moore MJ. 2004. Splicing enhances translation in mammalian cells: an additional function of the exon junction complex. Genes & Development 18: 210-222. doi: 10. 1101/gad. 1163204.
65. Nott A, Meislin SH, Moore MJ. 2003. A quantitative analysis of intron effects on mammalian gene expression. RNA 9: 607-617. doi: 10. 1261/rna. 5250403.
66. Nottrott S, Simard MJ, Richter JD. 2006. Human let-7a miRNA blocks protein production on actively translating polyribosomes. Nature Structural & Molecular Biology 13: 1108-1114. doi: 10. 1038/nsmb1173.
67. Olsen PH, Ambros V. 1999. The lin-4 regulatory RNA controls developmental timing in caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Developmental Biology 216: 671-680. doi: 10. 1006/dbio. 1999. 9523.
68. Parker R. 2012. RNA degradation in saccharomyces cerevisae. Genetics 191: 671-702. doi: 10. 1534/genetics. 111. 137265.
69. Piccirillo CA, Bjur E, Topisirovic I, Sonenberg N, Larsson O. 2014. Translational control of immune responses: from transcripts to translatomes. Nature Immunology 15: 503-511. doi: 10. 1038/ni. 2891.
70. Pisareva VP, Pisarev AV, Komar AA, Hellen CU, Pestova TV. 2008. Translation initiation on mammalian mRNAs with structured 5'UTRs requires DExH-box protein DHX29. Cell 135: 1237-1250. doi: 10. 1016/j. cell. 2008. 10. 037.
71. Popp MW, Maquat LE. 2013. Organizing principles of mammalian nonsense-mediated mRNA decay. Annual Review of Genetics 47: 139-165. doi: 10. 1146/annurev-genet-111212-133424.
72. Richter JD, Coller J. 2015. Pausing on polyribosomes: make way for elongation in translational control. Cell 163: 292-300. doi: 10. 1016/j. cell. 2015. 09. 041.
73. Roberts A, Trapnell C, Donaghey J, Rinn JL, Pachter L. 2011. Improving RNA-seq expression estimates by correcting for fragment bias. Genome Biology 12: R22. doi. doi: 10. 1186/gb-2011-12-3-r22.
74. Rouskin S, Zubradt M, Washietl S, Kellis M, Weissman JS. 2014. Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo. Nature 505: 701-705. doi: 10. 1038/nature12894.
75. Ruggero D. 2013. Translational control in cancer etiology. Cold Spring Harbor Perspectives in Biology 5: 1-27. doi: 10. 1101/cshperspect. a012336.
76. Sandberg R, Neilson JR, Sarma A, Sharp PA, Burge CB. 2008. Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites. Science 320: 1643-1647. doi: 10. 1126/science. 1155390.
77. Schwanhä usser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, Chen W, Selbach M. 2011. Global quantification of mammalian gene expression control. Nature 473: 337-342. doi: 10. 1038/nature10098.
78. Sen ND, Zhou F, Ingolia NT, Hinnebusch AG. 2015. Genome-wide analysis of translational efficiency reveals distinct but overlapping functions of yeast DEAD-box RNA helicases Ded1 and eIF4A. Genome Research 25: 1196-1205. doi: 10. 1101/gr. 191601. 115.
79. Sidrauski C, McGeachy AM, Ingolia NT, Walter P. 2015. The small molecule ISRIB reverses the effects of eIF2a phosphorylation on translation and stress granule assembly. eLife 4. doi: 10. 7554/eLife. 05033.
80. Soumillon M, Necsulea A, Weier M, Brawand D, Zhang X, Gu H, Barthè s P, Kokkinaki M, Nef S, Gnirke A, Dym M, de Massy B, Mikkelsen TS, Kaessmann H. 2013. Cellular source and mechanisms of high transcriptome complexity in the mammalian testis. Cell Reports 3: 2179-2190. doi: 10. 1016/j. celrep. 2013. 05. 031.
81. Spies N, Burge CB, Bartel DP. 2013. 3' UTR-isoform choice has limited influence on the stability and translational efficiency of most mRNAs in mouse fibroblasts. Genome Research 23: 2078-2090. doi: 10. 1101/gr. 156919. 113.
82. Spitale RC, Flynn RA, Zhang QC, Crisalli P, Lee B, Jung JW, Kuchelmeister HY, Batista PJ, Torre EA, Kool ET, Chang HY. 2015. Structural imprints in vivo decode RNA regulatory mechanisms. Nature 519: 486-490. doi: 10. 1038/nature14263.
83. Sterne-Weiler T, Martinez-Nunez RT, Howard JM, Cvitovik I, Katzman S, Tariq MA, Pourmand N, Sanford JR. 2013. Frac-seq reveals isoform-specific recruitment to polyribosomes. Genome Research 23: 1615-1623. doi: 10. 1101/gr. 148585. 112.
84. Swindell WR, Remmer HA, Sarkar MK, Xing X, Barnes DH, Wolterink L, Voorhees JJ, Nair RP, Johnston A, Elder JT, Gudjonsson JE. 2015. Proteogenomic analysis of psoriasis reveals discordant and concordant changes in mRNA and protein abundance. Genome Medicine 7: 86. doi: 10. 1186/s13073-015-0208-5.
85. Szostak E, Gebauer F. 2013. Translational control by 3'-UTR-binding proteins. Briefings in Functional Genomics 12: 58-65. doi: 10. 1093/bfgp/els056.
86. Tani H, Mizutani R, Salam KA, Tano K, Ijiri K, Wakamatsu A, Isogai T, Suzuki Y, Akimitsu N. 2012. Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals. Genome Research 22: 947-956. doi: 10. 1101/gr. 130559. 111.
87. Thermann R, Hentze MW. 2007. Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation. Nature 447: 875-878. doi: 10. 1038/nature05878.
88. Thorvaldsdó ttir H, Robinson JT, Mesirov JP. 2013. Integrative genomics viewer (iGV): high-performance genomics data visualization and exploration. Briefings in Bioinformatics 14: 178-192. doi: 10. 1093/bib/bbs017.
89. Trapnell C, Pachter L, Salzberg SL. 2009. TopHat: discovering splice junctions with RNA-seq. Bioinformatics 25: 1105-1111. doi: 10. 1093/bioinformatics/btp120.
90. Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, Salzberg SL, Wold BJ, Pachter L. 2010. Transcript assembly and quantification by RNA-seq reveals unannotated transcripts and isoform switching during cell differentiation. Nature Biotechnology 28: 511-515. doi: 10. 1038/nbt. 1621.
91. van Heesch S, van Iterson M, Jacobi J, Boymans S, Essers PB, de Bruijn E, Hao W, MacInnes AW, Cuppen E, Simonis M. 2014. Extensive localization of long noncoding RNAs to the cytosol and mono-and polyribosomal complexes. Genome Biology 15: R6. doi. doi: 10. 1186/gb-2014-15-1-r6.
92. Vassena R, Boue S, Gonzalez-Roca E, Aran B, Auer H, Veiga A, Belmonte JCI. 2011. Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development. Development 138: 3699-3709. doi: 10. 1242/dev. 064741.
93. Vogel C, Abreu RS, Ko D, Le SY, Shapiro BA, Burns SC, Sandhu D, Boutz DR, Marcotte EM, Penalva LO. 2010. Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line. Molecular Systems Biology 6: 400. doi: 10. 1038/msb. 2010. 59.
94. Wagner GP, Kin K, Lynch VJ. 2012. Measurement of mRNA abundance using RNA-seq data: RPKM measure is inconsistent among samples. Theory in Biosciences 131: 281-285. doi: 10. 1007/s12064-012-0162-3.
95. Walsh PS, Erlich HA, Higuchi R. 1992. Preferential PCR amplification of alleles: mechanisms and solutions. Genome Research 1: 241-250. doi: 10. 1101/gr. 1. 4. 241.
96. Wan J, Qian SB. 2014. TISdb: a database for alternative translation initiation in mammalian cells. Nucleic Acids Research 42: D845-D850. doi: 10. 1093/nar/gkt1085.
97. Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, Kingsmore SF, Schroth GP, Burge CB. 2008. Alternative isoform regulation in human tissue transcriptomes. Nature 456: 470-476. doi: 10. 1038/nature07509.
98. Warner JR, Rich A, Hall CE. 1962. Electron microscope studies of ribosomal clusters synthesizing hemoglobin. Science (New York, N. Y.) 138: 1399-1403. doi: 10. 1126/science. 138. 3548. 1399.
99. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ. 2010. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7: 618-630. doi: 10. 1016/j. stem. 2010. 08. 012.
100. Wickham H. 2009. Ggplot2. New York, NY: Springer New York. doi: 10. 1007/978-0-387-98141-3.
101. Wilczynska A, Bushell M. 2015. The complexity of miRNA-mediated repression. Cell Death and Differentiation 22: 22-33. doi: 10. 1038/cdd. 2014. 112.
102. Wolfe AL, Singh K, Zhong Y, Drewe P, Rajasekhar VK, Sanghvi VR, Mavrakis KJ, Jiang M, Roderick JE, Van der Meulen J, Schatz JH, Rodrigo CM, Zhao C, Rondou P, de Stanchina E, Teruya-Feldstein J, Kelliher MA, Speleman F, Porco JA, Pelletier J, Rä tsch G, Wendel HG. 2014. RNA g-quadruplexes cause eIF4A-dependent oncogene translation in cancer. Nature 513: 65-70. doi: 10. 1038/nature13485.
103. Wu S, Yu L. 2016. Targeting cullin-RING ligases for cancer treatment: rationales, advances and therapeutic implications. Cytotechnology 68: 1-8. doi: 10. 1007/s10616-015-9870-0.
104. Xie P, Zhang M, He S, Lu K, Chen Y, Xing G, Lu Y, Liu P, Li Y, Wang S, Chai N, Wu J, Deng H, Wang HR, Cao Y, Zhao F, Cui Y, Wang J, He F, Zhang L. 2014. The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis. Nature Communications 5: 3733. doi: 10. 1038/ncomms4733.
105. Xiong HY, Alipanahi B, Lee LJ, Bretschneider H, Merico D, Yuen RKC, Hua Y, Gueroussov S, Najafabadi HS, Hughes TR, Morris Q, Barash Y, Krainer AR, Jojic N, Scherer SW, Blencowe BJ, Frey BJ. 2015. The human splicing code reveals new insights into the genetic determinants of disease. Science 347: 1254806. doi: 10. 1126/science. 1254806.
106. Xue S, Tian S, Fujii K, Kladwang W, Das R, Barna M. 2015. RNA regulons in hox 5' UTRs confer ribosome specificity to gene regulation. Nature 517: 33-38. doi: 10. 1038/nature14010.
107. Yan L, Yang M, Guo H, Yang L, Wu J, Li R, Liu P, Lian Y, Zheng X, Yan J, Huang J, Li M, Wu X, Wen L, Lao K, Li R, Qiao J, Tang F. 2013. Single-cell RNA-seq profiling of human preimplantation embryos and embryonic stem cells. Nature Structural & Molecular Biology 20: 1131-1139. doi: 10. 1038/nsmb. 2660.
108. Zhang D, Zhao T, Ang HS, Chong P, Saiki R, Igarashi K, Yang H, Vardy LA. 2012. AMD1 is essential for ESC self-renewal and is translationally down-regulated on differentiation to neural precursor cells. Genes & Development 26: 461-473. doi: 10. 1101/gad. 182998. 111.
109. Zhang X, Gao X, Coots RA, Conn CS, Liu B, Qian SB. 2015. Translational control of the cytosolic stress response by mitochondrial ribosomal protein L18. Nature Structural & Molecular Biology 22: 404-410. doi: 10. 1038/nsmb. 3010.
110. Zhao W, Pollack JL, Blagev DP, Zaitlen N, McManus MT, Erle DJ. 2014. Massively parallel functional annotation of 3' untranslated regions. Nature Biotechnology 32: 387-391. doi: 10. 1038/nbt. 2851.
111. Zheng S, Black DL. 2013. Alternative pre-mRNA splicing in neurons: growing up and extending its reach. Trends in Genetics 29: 442-448. doi: 10. 1016/j. tig. 2013. 04. 003.