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Cited by 265RNA Research and SplicingRNA and protein synthesis mechanismsGenomics and Phylogenetic Studies

Tunable protein synthesis by transcript isoforms in human cells

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Floor, Stephen N, Doudna, Jennifer A·2016·eLife
DOI 10.7554/elife.10921PMC PMC4764583

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Abstract

Eukaryotic genes generate multiple RNA transcript isoforms though alternative transcription, splicing, and polyadenylation. However, the relationship between human transcript diversity and protein production is complex as each isoform can be translated differently. We fractionated a polysome profile and reconstructed transcript isoforms from each fraction, which we term Transcript Isoforms in Polysomes sequencing (TrIP-seq). Analysis of these data revealed regulatory features that control ribosome occupancy and translational output of each transcript isoform. We extracted a panel of 5′ and 3′ untranslated regions that control protein production from an unrelated gene in cells over a 100-fold range. Select 5′ untranslated regions exert robust translational control between cell lines, while 3′ untranslated regions can confer cell type-specific expression. These results expose the large dynamic range of transcript-isoform-specific translational control, identify isoform-specific sequences that control protein output in human cells, and demonstrate that transcript isoform diversity must be considered when relating RNA and protein levels.

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  • Polysome profiling has been used extensively to measure translation of native RNA isoforms, but isolating the role of 5′ UTR regulation has been difficult due to differences in the size and sequence of the concomitant coding sequences and 3′ UTRs.

    “Polysome profiling has been used extensively to measure translation of native RNA isoforms14,15 but isolating the role of 5′ UTR regulation has been difficult due to differences in the size and sequence of the concomitant coding sequences and 3′ UTRs.”

    From Human 5′ UTR design and variant effect prediction from a massively parallel translation assay (2019) · cites this paper as [14]

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  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 10.1038/nature06974 18496529 PMC2587346 · DOI · Paper page
  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 10.1073/pnas.0635171100 12660367 PMC153018 · DOI · Paper page
  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 10.1101/gr.150342.112 23580730 PMC3668365 · DOI
  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 10.1126/science.1230612 23258890 · DOI · Paper page
  5. Bartel DP 2009 MicroRNAs: target recognition and regulatory functions Cell 136 215 233 10.1016/j.cell.2009.01.002 19167326 PMC3794896 · DOI · Paper page
  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 e10921 10.1371/journal.pone.0037108 PMC3365017 22693568 · DOI
  7. 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 10.1038/nrm2548 19023284 · DOI
  8. Boutz PL Bhutkar A Sharp PA 2015 Detained introns are a novel, widespread class of post-transcriptionally spliced introns Genes & Development 29 63 80 10.1101/gad.247361.114 25561496 PMC4281565 · DOI
  9. 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 10.1126/science.1215110 22194413 PMC3414261 · DOI · Paper page
  10. 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 10.1016/j.bbagrm.2013.02.003 23428348 PMC3752887 · DOI
  11. 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 10.1073/pnas.0810916106 19372376 PMC2669787 · DOI · Paper page
  12. Chuang RY Weaver PL Liu Z Chang TH 1997 Requirement of the DEAD-box protein Ded1p for messenger RNA translation Science 275 1468 1471 10.1126/science.275.5305.1468 9045610 · DOI
  13. Cliff N 1993 Dominance statistics: ordinal analyses to answer ordinal questions Psychological Bulletin 114 494 509 10.1037/0033-2909.114.3.494 · DOI
  14. 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 10.1186/s13059-014-0559-z 25650959 PMC4302535 · DOI
  15. de Klerk E 't Hoen PA 2015 Alternative mRNA transcription, processing, and translation: insights from RNA sequencing Trends in Genetics: TIG 31 128 139 10.1016/j.tig.2015.01.001 25648499 · DOI · Paper page
  16. Ender C Krek A Friedländer 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 10.1016/j.molcel.2008.10.017 19026782 · DOI
  17. 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 10.1073/pnas.1305590110 23798422 PMC3710870 · DOI · Paper page
  18. 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 10.1098/rspb.2012.0153 22378807 PMC3350705 · DOI
  19. 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 e10921 10.3791/4140 PMC3471294 22782264 · DOI
  20. Fukaya T Tomari Y 2011 PABP is not essential for microRNA-mediated translational repression and deadenylation in vitro The EMBO Journal 30 4998 5009 10.1038/emboj.2011.426 22117217 PMC3243625 · DOI
  21. Galili T 2015 Dendextend: an r package for visualizing, adjusting and comparing trees of hierarchical clustering Bioinformatics 31 3718 3720 10.1093/bioinformatics/btv428 26209431 PMC4817050 · DOI
  22. 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 10.1038/nsmb.2115 PMC3190056 21909094 · DOI
  23. 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 10.1074/mcp.M111.014050 PMC3316730 22278370 · DOI · Paper page
  24. 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 10.1038/nmeth.1318 19363495 · DOI
  25. Godchaux W Adamson SD Herbert E 1967 Effects of cycloheximide on polyribosome function in reticulocytes Journal of Molecular Biology 27 57 72 10.1016/0022-2836(67)90351-8 6033612 · DOI
  26. 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 10.1128/MCB.14.4.2616 8139562 PMC358629 · DOI
  27. Göhring 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 10.1105/tpc.113.118075 24532591 PMC3967038 · DOI
  28. 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 10.1038/nmeth.2729 24213167 PMC4039304 · DOI
  29. 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 10.1016/S1097-2765(00)00108-8 11106749 · DOI
  30. Hinnebusch AG Lorsch JR 2012 The mechanism of eukaryotic translation initiation: new insights and challenges Cold Spring Harbor Perspectives in Biology 4 10.1101/cshperspect.a011544 PMC3475172 22815232 · DOI
  31. Hinnebusch AG 2005 Translational regulation of GCN4 and the general amino acid control of yeast Annual Review of Microbiology 59 407 450 10.1146/annurev.micro.59.031805.133833 16153175 · DOI
  32. 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 10.1016/j.celrep.2014.07.045 25159147 PMC4216110 · DOI
  33. 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 10.1126/science.1168978 19213877 PMC2746483 · DOI · Paper page
  34. Ingolia NT 2014 Ribosome profiling: new views of translation, from single codons to genome scale Nature Reviews Genetics 15 205 213 10.1038/nrg3645 24468696 · DOI
  35. Jangi M Boutz PL Paul P Sharp PA 2014 Rbfox2 controls autoregulation in RNA-binding protein networks Genes & Development 28 637 651 10.1101/gad.235770.113 24637117 PMC3967051 · DOI
  36. 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 10.1093/bioinformatics/bts251 22543366 PMC3381967 · DOI
  37. Jung H Gkogkas CG Sonenberg N Holt CE 2014 Remote control of gene function by local translation Cell 157 26 40 10.1016/j.cell.2014.03.005 24679524 PMC3988848 · DOI
  38. Kole R Krainer AR Altman S 2012 RNA therapeutics: beyond RNA interference and antisense oligonucleotides Nature Reviews. Drug Discovery 11 125 140 10.1038/nrd3625 22262036 PMC4743652 · DOI · Paper page
  39. 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 10.1128/MCB.00560-10 20837705 PMC2976371 · DOI
  40. Langmead B Salzberg SL 2012 Fast gapped-read alignment with bowtie 2 Nature Methods 9 357 359 10.1038/nmeth.1923 22388286 PMC3322381 · DOI · Paper page
  41. 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 10.1007/978-0-387-77374-2_12 18380348 · DOI
  42. 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 10.1186/1745-6150-9-3 24524654 PMC3937023 · DOI
  43. Lorenz R Bernhart SH Höner zu Siederdissen C Tafer H Flamm C Stadler PF Hofacker IL 2011 ViennaRNA package 2.0 Algorithms for Molecular Biology 6 26 10.1186/1748-7188-6-26 22115189 PMC3319429 · DOI · Paper page
  44. Love MI Huber W Anders S 2014 Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 Genome Biology 15 550 10.1186/s13059-014-0550-8 25516281 PMC4302049 · DOI · Paper page
  45. 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 10.4161/auto.21484 22874562 PMC3494597 · DOI
  46. 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 10.1038/nsmb1174 17128271 · DOI
  47. Maslon MM Heras SR Bellora N Eyras E Cáceres JF 2014 The translational landscape of the splicing factor SRSF1 and its role in mitosis eLife 3 10.7554/eLife.02028 PMC4027812 24842991 · DOI
  48. 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 10.1126/science.aaa0355 25954002 PMC4547472 · DOI · Paper page
  49. Merkin J Russell C Chen P Burge CB 2012 Evolutionary dynamics of gene and isoform regulation in mammalian tissues Science 338 1593 1599 10.1126/science.1228186 23258891 PMC3568499 · DOI · Paper page
  50. 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 10.1016/j.cub.2008.08.013 18818082 PMC2585380 · DOI
  51. 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 10.1002/wrna.1230 24687816 · DOI
  52. Müllner D 2013 fastcluster: fast hierarchical, agglomerative clustering routines for r and python Journal of Statistical Software 53 10.18637/jss.v053.i09 · DOI
  53. 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 10.1101/gad.1163204 14752011 PMC324426 · DOI
  54. Nott A Meislin SH Moore MJ 2003 A quantitative analysis of intron effects on mammalian gene expression RNA 9 607 617 10.1261/rna.5250403 12702819 PMC1370426 · DOI
  55. 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 10.1038/nsmb1173 17128272 · DOI
  56. 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 10.1006/dbio.1999.9523 10642801 · DOI · Paper page
  57. Parker R 2012 RNA degradation in saccharomyces cerevisae Genetics 191 671 702 10.1534/genetics.111.137265 22785621 PMC3389967 · DOI
  58. 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 10.1038/ni.2891 24840981 · DOI
  59. 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 10.1016/j.cell.2008.10.037 19109895 PMC2948571 · DOI
  60. Popp MW Maquat LE 2013 Organizing principles of mammalian nonsense-mediated mRNA decay Annual Review of Genetics 47 139 165 10.1146/annurev-genet-111212-133424 PMC4148824 24274751 · DOI
  61. Richter JD Coller J 2015 Pausing on polyribosomes: make way for elongation in translational control Cell 163 292 300 10.1016/j.cell.2015.09.041 26451481 PMC4600128 · DOI
  62. 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 10.1038/nature12894 24336214 PMC3966492 · DOI
  63. Ruggero D 2013 Translational control in cancer etiology Cold Spring Harbor Perspectives in Biology 5 1 27 10.1101/cshperspect.a012336 PMC3552512 22767671 · DOI
  64. 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 10.1126/science.1155390 18566288 PMC2587246 · DOI · Paper page
  65. 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 10.1101/gr.191601.115 26122911 PMC4510003 · DOI
  66. Sidrauski C McGeachy AM Ingolia NT Walter P 2015 The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly eLife 4 10.7554/eLife.05033 PMC4341466 25719440 · DOI
  67. Soumillon M Necsulea A Weier M Brawand D Zhang X Gu H Barthès 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 10.1016/j.celrep.2013.05.031 23791531 · DOI
  68. 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 10.1101/gr.156919.113 24072873 PMC3847777 · DOI
  69. 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 10.1038/nature14263 25799993 PMC4376618 · DOI
  70. 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 10.1101/gr.148585.112 23783272 PMC3787259 · DOI
  71. 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 10.1186/s13073-015-0208-5 26251673 PMC4527112 · DOI
  72. Szostak E Gebauer F 2013 Translational control by 3'-UTR-binding proteins Briefings in Functional Genomics 12 58 65 10.1093/bfgp/els056 23196851 PMC3548161 · DOI
  73. 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 10.1101/gr.130559.111 22369889 PMC3337439 · DOI
  74. Thermann R Hentze MW 2007 Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation Nature 447 875 878 10.1038/nature05878 17507927 · DOI
  75. Thorvaldsdóttir H Robinson JT Mesirov JP 2013 Integrative genomics viewer (iGV): high-performance genomics data visualization and exploration Briefings in Bioinformatics 14 178 192 10.1093/bib/bbs017 22517427 PMC3603213 · DOI · Paper page
  76. Trapnell C Pachter L Salzberg SL 2009 TopHat: discovering splice junctions with RNA-seq Bioinformatics 25 1105 1111 10.1093/bioinformatics/btp120 19289445 PMC2672628 · DOI
  77. 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 10.1186/gb-2014-15-1-r6 24393600 PMC4053777 · DOI
  78. 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 10.1242/dev.064741 21775417 PMC4074286 · DOI
  79. 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 10.1038/msb.2010.59 20739923 PMC2947365 · DOI · Paper page
  80. 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 10.1007/s12064-012-0162-3 22872506 · DOI
  81. Walsh PS Erlich HA Higuchi R 1992 Preferential PCR amplification of alleles: mechanisms and solutions Genome Research 1 241 250 10.1101/gr.1.4.241 1477658 · DOI
  82. Wan J Qian SB 2014 TISdb: a database for alternative translation initiation in mammalian cells Nucleic Acids Research 42 D845 D850 10.1093/nar/gkt1085 24203712 PMC3965020 · DOI
  83. 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 10.1038/nature07509 18978772 PMC2593745 · DOI · Paper page
  84. Warner JR Rich A Hall CE 1962 Electron microscope studies of ribosomal clusters synthesizing hemoglobin Science (New York, N.Y.) 138 1399 1403 10.1126/science.138.3548.1399 17753859 · DOI
  85. Wickham H 2009 Ggplot2 New York, NY Springer New York 10.1007/978-0-387-98141-3 · DOI · Paper page
  86. Wilczynska A Bushell M 2015 The complexity of miRNA-mediated repression Cell Death and Differentiation 22 22 33 10.1038/cdd.2014.112 25190144 PMC4262769 · DOI
  87. 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 Rätsch G Wendel HG 2014 RNA g-quadruplexes cause eIF4A-dependent oncogene translation in cancer Nature 513 65 70 10.1038/nature13485 25079319 PMC4492470 · DOI · Paper page
  88. Wu S Yu L 2016 Targeting cullin-RING ligases for cancer treatment: rationales, advances and therapeutic implications Cytotechnology 68 1 8 10.1007/s10616-015-9870-0 25899169 PMC4698256 · DOI
  89. 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 10.1038/ncomms4733 24821572 · DOI
  90. 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 10.1126/science.1254806 25525159 PMC4362528 · DOI
  91. 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 10.1038/nature14010 25409156 PMC4353651 · DOI
  92. 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 10.1038/nsmb.2660 23934149 · DOI · Paper page
  93. 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 10.1101/gad.182998.111 22391449 PMC3305984 · DOI
  94. 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 10.1038/nsmb.3010 PMC4424103 25866880 · DOI
  95. 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 10.1038/nbt.2851 PMC3981918 24633241 · DOI · Paper page
  96. Zheng S Black DL 2013 Alternative pre-mRNA splicing in neurons: growing up and extending its reach Trends in Genetics 29 442 448 10.1016/j.tig.2013.04.003 23648015 PMC3959871 · DOI · Paper page

Cited by

Sorted by citations

Authors
Floor, S. N., & Doudna, J. A.
Affiliations
Howard Hughes Medical Institute (US)
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2016-01-06
Volume
5
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.10921
PMC
PMC4764583
OpenAlex
W2226665541
Cited by
265
References
15
Citations by year
2026: 18 · 2025: 17 · 2024: 29 · 2023: 22 · 2022: 34 · 2021: 20 · 2020: 36 · 2019: 31 · 2018: 20 · 2017: 24 · 2016: 14
FWCI
12.67
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • Helen Hay Whitney Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
mRNA isoforms, alternative splicing, polyadenylation, translational regulation, ribosome occupancy, polysome profiling, 5' untranslated region, 3' untranslated region, cell type-specific gene expression, protein production
MeSH terms
Cell Line, Epithelial Cells, Gene Expression Regulation, Humans, Polyribosomes, RNA, Messenger, Protein Biosynthesis, Alternative Splicing, Protein Isoforms

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