Genome-wide functional analysis of human 5' untranslated region introns

Genome Biology

Volumn 11, Issue 3, 2010, Pages

  Cenik, Can ^a   Derti, Adnan ^a   Mellor, Joseph C ^a   Berriz, Gabriel F ^a   Roth, Frederick P ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b DANA FARBER CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN TYROSINE KINASE;

5' UNTRANSLATED REGION; ARTICLE; CONTROLLED STUDY; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE FUNCTION; GENOME ANALYSIS; INTRON; MOLECULAR EVOLUTION; REGULATOR GENE; VARIANCE; BIOLOGICAL MODEL; GENE EXPRESSION PROFILING; GENETICS; GENOMICS; HUMAN; METHODOLOGY;

5' UNTRANSLATED REGIONS; EVOLUTION, MOLECULAR; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENOMICS; HUMANS; INTRONS; MODELS, GENETIC; PROTEIN-TYROSINE KINASES;

EID: 77949449291     PISSN: 14747596     EISSN: 1474760X     Source Type: Journal    
DOI: 10.1186/gb-2010-11-3-r29     Document Type: Article

References (74)

1. Rodriguez-Trelles F, Tarrio R, Ayala FJ. Origins and evolution of spliceosomal introns. Annu Rev Genet 2006, 40:47-76. 10.1146/annurev.genet.40.110405.090625, 17094737.
2. Roy SW, Gilbert W. The evolution of spliceosomal introns: patterns, puzzles and progress. Nat Rev Genet 2006, 7:211-221.
3. Rogozin IB, Wolf YI, Sorokin AV, Mirkin BG, Koonin EV. Remarkable interkingdom conservation of intron positions and massive, lineage-specific intron loss and gain in eukaryotic evolution. Curr Biol 2003, 13:1512-1517. 10.1016/S0960-9822(03)00558-X, 12956953.
4. Carmel L, Rogozin IB, Wolf YI, Koonin EV. Patterns of intron gain and conservation in eukaryotic genes. BMC Evol Biol 2007, 7:192. 10.1186/1471-2148-7-192, 2151770, 17935625.
5. Lynch M, Conery JS. The origins of genome complexity. Science 2003, 302:1401-1404. 10.1126/science.1089370, 14631042.
6. Comeron JM, Kreitman M. The correlation between intron length and recombination in drosophila. Dynamic equilibrium between mutational and selective forces. Genetics 2000, 156:1175-1190. 1461334, 11063693.
7. Duret L. Why do genes have introns? Recombination might add a new piece to the puzzle. Trends Genet 2001, 17:172-175. 10.1016/S0168-9525(01)02236-3, 11275306.
8. Niu DK. Protecting exons from deleterious R-loops a potential advantage of having introns. Biol Direct 2007, 2:11. 10.1186/1745-6150-2-11, 1863416, 17459149.
9. Blencowe BJ. Alternative splicing: new insights from global analyses. Cell 2006, 126:37-47. 10.1016/j.cell.2006.06.023, 16839875.
10. Xing Y, Lee C. Alternative splicing and RNA selection pressure - evolutionary consequences for eukaryotic genomes. Nat Rev Genet 2006, 7:499-510. 10.1038/nrg1896, 16770337.
11. Matlin AJ, Clark F, Smith CW. Understanding alternative splicing: towards a cellular code. Nat Rev Mol Cell Biol 2005, 6:386-398. 10.1038/nrm1645, 15956978.
12. Johnson JM, Castle J, Garrett-Engele P, Kan Z, Loerch PM, Armour CD, Santos R, Schadt EE, Stoughton R, Shoemaker DD. Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science 2003, 302:2141-2144. 10.1126/science.1090100, 14684825.
13. Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, Kingsmore SF, Schroth GP, Burge CB. Alternative isoform regulation in human tissue transcriptomes. Nature 2008, 456:470-476. 10.1038/nature07509, 2593745, 18978772.
14. Castle JC, Zhang C, Shah JK, Kulkarni AV, Kalsotra A, Cooper TA, Johnson JM. Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines. Nat Genet 2008, 40:1416-1425. 10.1038/ng.264, 18978788.
15. Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet 2008, 40:1413-1415. 10.1038/ng.259, 18978789.
16. Wang Z, Burge CB. Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA 2008, 14:802-813. 10.1261/rna.876308, 2327353, 18369186.
17. Sugnet CW, Srinivasan K, Clark TA, O'Brien G, Cline MS, Wang H, Williams A, Kulp D, Blume JE, Haussler D, Ares M. Unusual intron conservation near tissue-regulated exons found by splicing microarrays. PLoS Comput Biol 2006, 2:e4. 10.1371/journal.pcbi.0020004, 1331982,1331982, 16424921.
18. Pesole G, Mignone F, Gissi C, Grillo G, Licciulli F, Liuni S. Structural and functional features of eukaryotic mRNA untranslated regions. Gene 2001, 276:73-81. 11591473, 10.1016/S0378-1119(01)00674-6.
19. Hong X, Scofield DG, Lynch M. Intron size, abundance, and distribution within untranslated regions of genes. Mol Biol Evol 2006, 23:2392-2404. 10.1093/molbev/msl111, 16980575.
20. Chang YF, Imam JS, Wilkinson MF. The nonsense-mediated decay RNA surveillance pathway. Annu Rev Biochem 2007, 76:51-74. 10.1146/annurev.biochem.76.050106.093909, 17352659.
21. Maquat LE. Nonsense-mediated mRNA decay in mammals. J Cell Sci 2005, 118:1773-1776. 10.1242/jcs.01701, 15860725.
22. Scofield DG, Hong X, Lynch M. Position of the final intron in full-length transcripts: determined by NMD?. Mol Biol Evol 2007, 24:896-899. 10.1093/molbev/msm010, 17244600.
23. Castillo-Davis CI, Mekhedov SL, Hartl DL, Koonin EV, Kondrashov FA. Selection for short introns in highly expressed genes. Nat Genet 2002, 31:415-418.
24. Urritia AO, Hurst LD. The signature of selection mediated by expression on human genes. Genome Res 2003, 13:2260-2264. 10.1101/gr.641103, 403694, 12975314.
25. Duret L, Mouchiroud D. Expression pattern and, surprisingly, gene length, shape codon usage in Caenorhabditis, Drosophila, and Arabidopsis. Proc Natl Acad Sci USA 1999, 96:4482-4487. 10.1073/pnas.96.8.4482, 16358, 10200288.
26. Ren X-Y, Vorst O, Fiers MWEJ, Stiekema WJ, Nap J-P. In plants, highly expressed genes are the least compact. Trends Genet 2006, 22:528-532. 10.1016/j.tig.2006.08.008, 16934358.
27. Vinogradov AE. 'Genome design' model and multicellular complexity: golden middle. Nucleic Acids Res 2006, 34:5906-5914. 10.1093/nar/gkl773, 1635334, 17062620.
28. Eisenberg E, Levanon EY. Human housekeeping genes are compact. Trends Genet 2003, 19:362-366. 10.1016/S0168-9525(03)00140-9, 12850439.
29. Vinogradov AE. Compactness of human housekeeping genes: selection for economy or genomic design?. Trends Genet 2004, 20:248-253. 10.1016/j.tig.2004.03.006, 15109779.
30. Vinogradov AE. 'Genome design' model: evidence from conserved intronic sequence in human-mouse comparison. Genome Res 2006, 16:347-354. 10.1101/gr.4318206, 1415212, 16461636.
31. Chen J, Sun M, Hurst LD, Carmichael GG, Rowley JD. Human antisense genes have unusually short introns: evidence for selection for rapid transcription. Trends Genet 2005, 21:203-207. 10.1016/j.tig.2005.02.003, 15797613.
32. Chen J, Sun M, Rowley JD, Hurst LD. The small introns of antisense genes are better explained by selection for rapid transcription than by 'genomic design'. Genetics 2005, 171:2151-2155. 10.1534/genetics.105.048066, 1456133, 16143605.
33. Chamary J-V, Hurst LD. Similar rates but different modes of sequence evolution in introns and at exonic silent sites in rodents evidence for selectively driven codon usage. Mol Biol Evol 2004, 21:1014-1023. 10.1093/molbev/msh087, 15014158.
34. Majewski J, Ott J. Distribution and characterization of regulatory elements in the human genome. Genome Res 2002, 12:1827-1836. 10.1101/gr.606402, 187578, 12466286.
35. Hughes SS, Buckley CO, Neafsey DE. Complex selection on intron size in Cryptococcus. Mol Biol Evol 2008, 25:247-253. 10.1093/molbev/msm220, 18171915.
36. Roy SW, Penny D, Neafsey DE. Evolutionary conservation of UTR intron boundaries in Cryptococcus. Mol Biol Evol 2007, 24:1140-1148. 10.1093/molbev/msm045, 17374879.
37. Eden E, Brunak S. Analysis and recognition of 5'UTR intron splice sites in human pre-mRNA. Nucleic Acids Res 2004, 32:1131-1142. 10.1093/nar/gkh273, 373407, 14960723.
38. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, et al. The sequence of the human genome. Science 2001, 291:1304-1351. 10.1126/science.1058040, 11181995.
39. Thattai M, van Oudenaarden A. Intrinsic noise in gene regulatory networks. Proc Natl Acad Sci USA 2001, 98:8614-8619. 10.1073/pnas.151588598, 37484, 11438714.
40. Berriz GF, King OD, Bryant B, Sander C, Roth FP. Characterizing gene sets with FuncAssociate. Bioinformatics 2003, 19:2502-2504. 10.1093/bioinformatics/btg363, 14668247.
41. Beißbarth T, Speed TP. GOstat: find statistically overrepresented Gene Ontologies within a group of genes. Bioinformatics 2004, 20:1464-1465. 10.1093/bioinformatics/bth088, 14962934.
42. Berriz GF, Roth FP. The Synergizer service for translating gene, protein and other biological identifiers. Bioinformatics 2008, 24:2272-2273. 10.1093/bioinformatics/btn424, 2553440, 18697767.
43. Tsygankov AY. Non-receptor protein tyrosine kinases. Front Biosci 2003, 8:s595-635. 10.2741/1106, 12700079.
44. King DC, Taylor J, Elnitski L, Chiaromonte F, Miller W, Hardison RC. Evaluation of regulatory potential and conservation scores for detecting cis-regulatory modules in aligned mammalian genome sequences. Genome Res 2005, 15:1051-1060. 10.1101/gr.3642605, 1182217, 16024817.
45. Siddharthan R, Siggia ED, Nimwegen E. PhyloGibbs: aGibbs sampling motif finder that incorporates phylogeny. PloS Comput Biol 2005, 1:e67. 10.1371/journal.pcbi.0010067, 1309704,1309704, 16477324.
46. Xie X, Lu J, Kulbokas EJ, Golub TR, Mootha V, Lindblad-Toh K, Lander ES, Kellis M. Systematic discovery of regulatory motifs in human promoters and 30 UTRs by comparison of several mammals. Nature 2005, 434:338-345. 10.1038/nature03441, 15735639.
47. Mahony S, Benos PV. STAMP: a web tool for exploring DNA-binding motif similarities. Nucleic Acids Res 2007, 35:W253-258. 10.1093/nar/gkm272, 1933206, 17478497.
48. Furger A, O'Sullivan JM, Binnie A, Lee BA, Proudfout NJ. Promoter proximal splice sites enhance transcription. Genes Dev 2002, 16:2792-2799. 10.1101/gad.983602, 187476, 12414732.
49. Brinster RL, Allen JM, Behringer RR, Gelinas RE, Palmiter RD. Introns increase transcriptional efficiency in transgenic mice. Proc Natl Acad Sci USA 1988, 85:836-840. 10.1073/pnas.85.3.836, 279650, 3422466.
50. Palmiter RD, Sandgren EP, Avarbock MR, Allen DD, Brinster RL. Heterologous introns can enhance expression of transgenes in mice. Proc Natl Acad Sci USA 1991, 88:478-482. 10.1073/pnas.88.2.478, 50834, 1988947.
51. Jonsson JJ, Foresman MD, Wilson N, McIvor RS. Intron requirement for expression of the human purine nucleoside phosphorylase gene. Nucleic Acids Res 1992, 20:3191-3198. 10.1093/nar/20.12.3191, 312458, 1620616.
52. Le Hir H, Nott A, Moore MJ. How introns influence and enhance eukaryotic gene expression. Trends Biochem Sci 2003, 28:215-220. 10.1016/S0968-0004(03)00052-5, 12713906.
53. Rose AB. The effect of intron location on intron-mediated enhancement of gene expression in Arabidopsis. Plant J 2004, 40:744-751. 10.1111/j.1365-313X.2004.02247.x, 15546357.
54. Rose AB, Elfersi T, Parra G, Korf I. Promoter-proximal introns in Arabidopsis thaliana are enriched in dispersed signals that elevate gene expression. Plant Cell 2008, 20:543-551. 10.1105/tpc.107.057190, 2329928, 18319396.
55. Fong YW, Zhou Q. Stimulatory effect of splicing factors on transcriptional elongation. Nature 2001, 414:929-933. 10.1038/414929a, 11780068.
56. Chan RY, Boudreau-Lariviere C, Angus LM, Mankal FA, Jasmin BJ. An intronic enhancer containing an N-box motif is required for synapse- and tissue-specific expression of the acetylcholinesterase gene in skeletal muscle fibers. Proc Natl Acad Sci USA 1999, 96:4627-4632. 10.1073/pnas.96.8.4627, 16383, 10200313.
57. Lu J, Sivamani E, Azhakanandam K, Samadder P, Li X, Qu R. Gene expression enhancement mediated by the 5' UTR intron of the rice rubi3 gene varied remarkably among tissues in transgenic rice plants. Mol Genet Genomics 2008, 279:563-572. 10.1007/s00438-008-0333-6, 18320227.
58. Rohrer J, Conley ME. Transcriptional regulatory elements within the first intron of Bruton's tyrosine kinase. Blood 1998, 91:214-221.
59. Smith L. Post-transcriptional regulation of gene expression by alternative 5'-untranslated regions in carcinogenesis. Biochem Soc Trans 2008, 36:708-711. 10.1042/BST0360708, 18631145.
60. Rosenstiel P, Huse K, Franke A, Hampe J, Reichwald K, Platzer C, Roberts RG, Mathew CG, Platzer M, Schreiber S. Functional characterization of two novel 5' untranslated exons reveals a complex regulation of NOD2 protein expression. BMC Genomics 2007, 8:472. 10.1186/1471-2164-8-472, 2228316, 18096043.
61. Araud T, Genolet R, Jaquier-Gubler P, Curran J. Alternatively spliced isoforms of the human elk-1 mRNA within the 5' UTR implications for ELK-1 expression. Nucleic Acids Res 2007, 35:4649-4663. 10.1093/nar/gkm482, 1950554, 17591614.
62. Ma XM, Yoon S-O, Richardson CJ, Julich K, Blenis J. SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs. Cell 2008, 133:303-313. 10.1016/j.cell.2008.02.031, 18423201.
63. Pruitt KD, Tatusova T, Maglott DR. NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res 2007, 35:D61-D65. 10.1093/nar/gkl842, 1716718, 17130148.
64. Rhead B, Karolchik D, Kuhn RM, Hinrichs AS, Zweig AS, Fujita PA, Diekhans M, Smith KE, Rosenbloom KR, Raney BJ, Pohl A, Pheasant M, Meyer LR, Learned K, Hsu F, Hillman-Jackson J, Harte RA, Giardine B, Dreszer TR, Clawson H, Barber GP, Haussler D, Kent WJ. The UCSC Genome Browser database: update 2010. Nucleic Acids Res 2010, 38:D613-D619. 10.1093/nar/gkp939, 2808870, 19906737.
65. Giardine B, Riemer C, Hardison RC, Burhans R, Elnitski L, Shah P, Zhang Y, Blankenberg D, Albert I, Taylor J, Miller W, Kent WJ, Nekrutenko A. Galaxy: a platform for interactive large-scale genome analysis. Genome Res 2005, 15:1451-1455. 10.1101/gr.4086505, 1240089, 16169926.
66. Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, Cooke MP, Walker JR, Hogenesch JB. A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci USA 2004, 101:6062-6067. 10.1073/pnas.0400782101, 395923, 15075390.
67. hexbin: Hexagonal Binning Routines. R package version 1.18.0. , http://www.bioconductor.org/packages/bioc/html/hexbin.html
68. Zeileis A, Grothendieck G. zoo: S3 Infrastructure for Regular and Irregular Time Series. J Stat Software 2005, 14:1-27.
69. HomoloGene. , http://www.ncbi.nlm.nih.gov/homologene
70. Altenhoff AM, Dessimoz C. Phylogenetic and functional assessment of orthologs inference projects and methods. PLoS Comput Biol 2009, 5:e1000262. 10.1371/journal.pcbi.1000262, 2612752, 19148271.
71. UCSC Genome Browser LiftOver Utility. , http://genome.ucsc.edu/cgi-bin/hgLiftOver
72. Siddharthan R, Nimwegen E. Detecting regulatory sites using PhyloGibbs. Methods in Molecular Biology 2007, 382-402. Bergman NH: Humana Press.
73. Barrell D, Dimmer E, Huntley RP, Binns D, O'Donovan C, Apweiler R. The GOA database in 2009 - an integrated Gene Ontology Annotation resource. Nucleic Acids Res 2009, 37:D396-D403. 10.1093/nar/gkn803, 2686469, 18957448.
74. Sandelin A, Wasserman WW. Constrained binding site diversity within families of transcription factors enhances pattern discovery bioinformatics. J Mol Biol 2004, 338:207-215. 10.1016/j.jmb.2004.02.048, 15066426.