Unmasking alternative splicing inside protein-coding exons defines exitrons and their role in proteome plasticity

Genome Research

Volumn 25, Issue 7, 2015, Pages 995-1007

  Marquez, Yamile ^a   Höpfler, Markus ^a,c   Ayatollahi, Zahra ^a   Barta, Andrea ^a   Kalyna, Maria ^a,b  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b UNIVERSITY OF NATURAL RESOURCES AND LIFE SCIENCES   (Austria)

^c MAX PLANCK INSTITUTE OF BIOCHEMISTRY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

INITIATION FACTOR 4A; NUCLEOTIDE; PROTEOME; RNA HELICASE; SERINE ARGININE RICH PROTEIN; TRANSCRIPTOME;

ACETYLATION; ALTERNATIVE RNA SPLICING; AMINO ACID SEQUENCE; ARABIDOPSIS; ARABIDOPSIS LYRATA; ARTICLE; BINDING SITE; BREAST CANCER; CAENORHABDITIS ELEGANS; CYTOPLASM; DNA BASE COMPOSITION; DNA BINDING; EVOLUTION; EVOLUTIONARY ADAPTATION; EXITRON; EXON; FLOWER; GENE DUPLICATION; GENE ONTOLOGY; GENE STRUCTURE; GENETIC RECOMBINATION; GENETIC VARIABILITY; HUMAN; HUMAN TISSUE; INTRON; NITROSYLATION; NONHUMAN; PLASTICITY; PRIORITY JOURNAL; PROTEIN CODING EXON; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; REGULATORY MECHANISM; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SEEDLING; STOP CODON; STRESS; SUMOYLATION; UBIQUITINATION; ANTIBODY SPECIFICITY; BREAST TUMOR; FEMALE; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MOLECULAR EVOLUTION; OPEN READING FRAME; PHYSIOLOGICAL STRESS; PROTEIN SYNTHESIS; PROTEOMICS; RNA TRANSPORT;

ANIMALIA; ARABIDOPSIS;

ALTERNATIVE SPLICING; ARABIDOPSIS; BREAST NEOPLASMS; EVOLUTION, MOLECULAR; EXONS; FEMALE; GENE EXPRESSION REGULATION, PLANT; HUMANS; INTRONS; OPEN READING FRAMES; ORGAN SPECIFICITY; PROTEIN BIOSYNTHESIS; PROTEOMICS; RNA TRANSPORT; STRESS, PHYSIOLOGICAL; TRANSCRIPTOME;

EID: 84937031603     PISSN: 10889051     EISSN: 15495469     Source Type: Journal    
DOI: 10.1101/gr.186585.114     Document Type: Article

References (69)

1. Baerenfaller K, Grossmann J, Grobei MA, Hull R, Hirsch-Hoffmann M, Yalovsky S, Zimmermann P, Grossniklaus U, Gruissem W, Baginsky S. 2008. Genome-scale proteomics reveals Arabidopsis thaliana gene models and proteome dynamics. Science 320: 938-941.
2. Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, Ren J, Li WW, Noble WS. 2009. MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res 37: W202-W208.
3. Bolle C, Huep G, Kleinbolting N, Haberer G, Mayer K, Leister D, Weisshaar B. 2013. GABI-DUPLO: a collection of double mutants to overcome genetic redundancy in Arabidopsis thaliana. Plant J 75: 157-171.
4. Barbosa-Morais NL, Irimia M, Pan Q, Xiong HY, Gueroussov S, Lee LJ, Slobodeniuc V, Kutter C, Watt S, Colak R, et al. 2012. The evolutionary landscape of alternative splicing in vertebrate species. Science 338: 1587-1593.
5. Bonnal S, Martinez C, Forch P, Bachi A, Wilm M, Valcarcel J. 2008. RBM5/Luca-15/H37 regulates Fas alternative splice site pairing after exon definition. Mol Cell 32: 81-95.
6. Boothby TC, Zipper RS, van der Weele CM, Wolniak SM. 2013. Removal of retained introns regulates translation in the rapidly developing gametophyte of Marsilea vestita. Dev Cell 24: 517-529.
7. Braunschweig U, Gueroussov S, Plocik AM, Graveley BR, Blencowe BJ. 2013. Dynamic integration of splicing within gene regulatory pathways. Cell 152: 1252-1269.
8. Braunschweig U, Barbosa-Morais NL, Pan Q, Nachman EN, Alipanahi B, Gonatopoulos-Pournatzis T, Frey B, Irimia M, Blencowe BJ. 2014. Widespread intron retention in mammals functionally tunes transcriptomes. Genome Res 24: 1774-1786.
9. Brosch M, Saunders GI, Frankish A, Collins MO, Yu L, Wright J, Verstraten R, Adams DJ, Harrow J, Choudhary JS, et al. 2011. Shotgun proteomics aids discovery of novel protein-coding genes, alternative splicing, and "resurrected"pseudogenes in the mouse genome. Genome Res 21: 756-767.
10. Buljan M, Chalancon G, Eustermann S, Wagner GP, Fuxreiter M, Bateman A, Babu MM. 2012. Tissue-specific splicing of disordered segments that embed binding motifs rewires protein interaction networks. Mol Cell 46: 871-883.
11. Buljan M, Chalancon G, Dunker AK, Bateman A, Balaji S, Fuxreiter M, Babu MM. 2013. Alternative splicing of intrinsically disordered regions and rewiring of protein interactions. Curr Opin Struct Biol 23: 443-450.
12. Castellana NE, Payne SH, Shen Z, Stanke M, Bafna V, Briggs SP. 2008. Discovery and revision of Arabidopsis genes by proteogenomics. Proc Natl Acad Sci 105: 21034-21038.
13. Catania F, Lynch M. 2008.Where do introns come from? PLoS Biol 6: e283.
14. Cordin O, Banroques J, Tanner NK, Linder P. 2006. The DEAD-box protein family of RNA helicases. Gene 367: 17-37.
15. Dahmcke CM, Buchmann-Moller S, Jensen NA, Mitchelmore C. 2008. Altered splicing in exon 8 of the DNA replication factor CIZ1 affects subnuclear distribution and is associated with Alzheimer's disease. Mol Cell Neurosci 38: 589-594.
16. Dosztanyi Z, Csizmok V, Tompa P, Simon I. 2005. IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content. Bioinformatics 21: 3433-3434.
17. Dosztanyi Z, Meszaros B, Simon I. 2009. ANCHOR: web server for predicting protein binding regions in disordered proteins. Bioinformatics 25: 2745-2746.
18. Duvick J, Fu A, Muppirala U, Sabharwal M, Wilkerson MD, Lawrence CJ, Lushbough C, Brendel V. 2008. PlantGDB: a resource for comparative plant genomics. Nucleic Acids Res 36: D959-D965.
19. Elliott DJ, Grellscheid SN. 2006. Alternative RNA splicing regulation in the testis. Reproduction 132: 811-819.
20. Eswaran J, Horvath A, Godbole S, Reddy SD, Mudvari P, Ohshiro K, Cyanam D, Nair S, Fuqua SA, Polyak K, et al. 2013. RNA sequencing of cancer reveals novel splicing alterations. Sci Rep 3: 1689.
21. Fairbrother WG, Holste D, Burge CB, Sharp PA. 2004. Single nucleotide polymorphism-based validation of exonic splicing enhancers. PLoS Biol 2: E268.
22. Finn RD, Clements J, Eddy SR. 2011. HMMER web server: interactive sequence similarity searching. Nucleic Acids Res 39: W29-W37.
23. Flicek P, Ahmed I, Amode MR, Barrell D, Beal K, Brent S, Carvalho-Silva D, Clapham P, Coates G, Fairley S, et al. 2013. Ensembl 2013. Nucleic Acids Res 41: D48-D55.
24. Fushimi K, Ray P, Kar A, Wang L, Sutherland LC, Wu JY. 2008. Up-regulation of the proapoptotic caspase 2 splicing isoform by a candidate tumor suppressor, RBM5. Proc Natl Acad Sci 105: 15708-15713.
25. 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. Plant Cell 26: 754-764.
26. Good PJ, Chen Q, Warner SJ, Herring DC. 2000. A family of human RNA-binding proteins related to the Drosophila Bruno translational regulator. J Biol Chem 275: 28583-28592.
27. Hatton AR, Subramaniam V, Lopez AJ. 1998. Generation of alternative ultra-bithorax isoforms and stepwise removal of a large intron by resplicing at exon-exon junctions. Mol Cell 2: 787-796.
28. Irimia M, Rukov JL, Penny D, Vinther J, Garcia-Fernandez J, Roy SW. 2008. Origin of introns by 'intronization' of exonic sequences. Trends Genet 24: 378-381.
29. Jaillon O, Bouhouche K, Gout JF, Aury JM, Noel B, Saudemont B, Nowacki M, Serrano V, Porcel BM, Segurens B, et al. 2008. Translational control of intron splicing in eukaryotes. Nature 451: 359-362.
30. Kalsotra A, Cooper TA. 2011. Functional consequences of developmentally regulated alternative splicing. Nat Rev Genet 12: 715-729.
31. Kalyna M, Simpson CG, Syed NH, Lewandowska D, Marquez Y, Kusenda B, Marshall J, Fuller J, Cardle L, McNicol J, et al. 2012. Alternative splicing and nonsense-mediated decay modulate expression of important regulatory genes in Arabidopsis. Nucleic Acids Res 40: 2454-2469.
32. Kan Z, Garrett-Engele PW, Johnson JM, Castle JC. 2005. Evolutionarily conserved and diverged alternative splicing events show different expression and functional profiles. Nucleic Acids Res 33: 5659-5666.
33. Kang LF, Zhu ZL, Zhao Q, Chen LY, Zhang Z. 2012. Newly evolved introns in human retrogenes provide novel insights into their evolutionary roles. BMC Evol Biol 12: 128.
34. Kelemen O, Convertini P, Zhang Z, Wen Y, Shen M, Falaleeva M, Stamm S. 2013. Function of alternative splicing. Gene 514: 1-30.
35. Kim HS, Abbasi N, Choi SB. 2013. Bruno-like proteins modulate flowering time via 3′ UTR-dependent decay of SOC1 mRNA. New Phytol 198: 747-756.
36. Leviatan N, Alkan N, Leshkowitz D, Fluhr R. 2013. Genome-wide survey of cold stress regulated alternative splicing in Arabidopsis thaliana with tiling microarray. PLoS One 8: e66511.
37. Lim LP, Burge CB. 2001. A computational analysis of sequence features involved in recognition of short introns. Proc Natl Acad Sci 98: 11193-11198.
38. Liu M, Grigoriev A. 2004. Protein domains correlate strongly with exons in multiple eukaryotic genomes: evidence of exon shuffling? Trends Genet 20: 399-403.
39. Lukic S, Nicolas JC, Levine AJ. 2014. The diversity of zinc-finger genes on human chromosome 19 provides an evolutionary mechanism for defense against inherited endogenous retroviruses. Cell Death Differ 21: 381-387.
40. Marinescu V, Loomis PA, Ehmann S, Beales M, Potashkin JA. 2007. Regulation of retention of FosB intron 4 by PTB. PLoS One 2: e828.
41. Marquez Y, Brown JW, Simpson C, Barta A, Kalyna M. 2012. Transcriptome survey reveals increased complexity of the alternative splicing landscape in Arabidopsis. Genome Res 22: 1184-1195.
42. Merkin J, Russell C, Chen P, Burge CB. 2012. Evolutionary dynamics of gene and isoform regulation in mammalian tissues. Science 338: 1593-1599.
43. Milde-Langosch K, Kappes H, Riethdorf S, Loning T, Bamberger AM. 2003. FosB is highly expressed in normal mammary epithelia, but down-regulated in poorly differentiated breast carcinomas. Breast Cancer Res Treat 77: 265-275.
44. Ner-Gaon H, Halachmi R, Savaldi-Goldstein S, Rubin E, Ophir R, Fluhr R. 2004. Intron retention is a major phenomenon in alternative splicing in Arabidopsis. Plant J 39: 877-885.
45. O'Bryan MK, Clark BJ, McLaughlin EA, D'Sylva RJ, O'Donnell L, Wilce JA, Sutherland J, O'Connor AE, Whittle B, Goodnow CC, et al. 2013. RBM5 is a male germ cell splicing factor and is required for spermatid differentiation and male fertility. PLoS Genet 9: e1003628.
46. O'Toole N, Hattori M, Andres C, Iida K, Lurin C, Schmitz-Linneweber C, Sugita M, Small I. 2008. On the expansion of the pentatricopeptide repeat gene family in plants. Mol Biol Evol 25: 1120-1128.
47. Obradovic Z, Peng K, Vucetic S, Radivojac P, Dunker AK. 2005. Exploiting heterogeneous sequence properties improves prediction of protein disorder. Proteins 61: 176-182.
48. Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. 2008. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet 40: 1413-1415.
49. Peng K, Radivojac P, Vucetic S, Dunker AK, Obradovic Z. 2006. Length-dependent prediction of protein intrinsic disorder. BMC Bioinformatics 7: 208.
50. Reddy AS, Marquez Y, Kalyna M, Barta A. 2013. Complexity of the alternative splicing landscape in plants. Plant Cell 25: 3657-3683.
51. Reed R, Maniatis T. 1986. A role for exon sequences and splice-site proximity in splice-site selection. Cell 46: 681-690.
52. Roca X, Sachidanandam R, Krainer AR. 2003. Intrinsic differences between authentic and cryptic 5? splice sites. Nucleic Acids Res 31: 6321-6333.
53. Roy SW, Gilbert W. 2006. The evolution of spliceosomal introns: patterns, puzzles and progress. Nat Rev Genet 7: 211-221.
54. Shalgi R, Hurt JA, Lindquist S, Burge CB. 2014. Widespread inhibition of posttranscriptional splicing shapes the cellular transcriptome following heat shock. Cell Rep 7: 1362-1370.
55. Song Z, Wu P, Ji P, Zhang J, Gong Q, Wu J, Shi Y. 2012. Solution structure of the second RRM domain of RBM5 and its unusual binding characters for different RNA targets. Biochemistry 51: 6667-6678.
56. Srebrow A, Kornblihtt AR. 2006. The connection between splicing and cancer. J Cell Sci 119(Pt 13): 2635-2641.
57. Staiger D, Brown JW. 2013. Alternative splicing at the intersection of biological timing, development, and stress responses. Plant Cell 25: 3640-3656.
58. Sugliani M, Brambilla V, Clerkx EJ, Koornneef M, Soppe WJ. 2010. The conserved splicing factor SUA controls alternative splicing of the developmental regulator ABI3 in Arabidopsis. Plant Cell 22: 1936-1946.
59. Syed NH, Kalyna M, Marquez Y, Barta A, Brown JW. 2012. Alternative splicing in plants: coming of age. Trends Plant Sci 17: 616-623.
60. Tomita M, Shimizu N, Brutlag DL. 1996. Introns and reading frames: correlation between splicing sites and their codon positions. Mol Biol Evol 13: 1219-1223.
61. Wang Z, Burge CB. 2008. Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA 14: 802-813.
62. 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.
63. Wilhelm M, Schlegl J, Hahne H, Moghaddas Gholami A, Lieberenz M, Savitski MM, Ziegler E, Butzmann L, Gessulat S, Marx H, et al. 2014. Mass-spectrometry-based draft of the human proteome. Nature 509: 582-587.
64. Wong JJ, Ritchie W, Ebner OA, Selbach M, Wong JW, Huang Y, Gao D, Pinello N, Gonzalez M, Baidya K, et al. 2013. Orchestrated intron retention regulates normal granulocyte differentiation. Cell 154: 583-595.
65. Yap K, Lim ZQ, Khandelia P, Friedman B, Makeyev EV. 2012. Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention. Genes Dev 26: 1209-1223.
66. Yeo G, Holste D, Kreiman G, Burge CB. 2004. Variation in alternative splicing across human tissues. Genome Biol 5: R74.
67. Zhang C, Frias MA, Mele A, Ruggiu M, Eom T, Marney CB, Wang H, Licatalosi DD, Fak JJ, Darnell RB. 2010. Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls. Science 329: 439-443.
68. Zheng Q, Wang XJ. 2008. GOEAST: a web-based software toolkit for Gene Ontology enrichment analysis. Nucleic Acids Res 36: W358-W363.
69. Zhu Z, Zhang Y, Long M. 2009. Extensive structural renovation of retrogenes in the evolution of the Populus genome. Plant Physiol 151: 1943-1951.