A complex network of factors with overlapping affinities represses splicing through intronic elements

Nature Structural and Molecular Biology

Volumn 20, Issue 1, 2013, Pages 36-45

  Wang, Yang ^a   Xiao, Xinshu ^b,c   Zhang, Jianming ^b,d   Choudhury, Rajarshi ^a   Robertson, Alex ^b   Li, Kai ^a   Ma, Meng ^a,e   Burge, Christopher B ^b   Wang, Zefeng ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e ANHUI UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA; OLIGONUCLEOTIDE;

ARTICLE; CELL STRAIN HEK293; EXON; FEMALE; FLUORESCENCE ACTIVATED CELL SORTING; HELA CELL; HUMAN; HUMAN CELL; INTRON; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN RNA BINDING; RNA SEQUENCE; RNA SPLICING;

BASE COMPOSITION; CELL LINE; HEK293 CELLS; HELA CELLS; HUMANS; INTRONS; RNA INTERFERENCE; RNA PRECURSORS; RNA SPLICING; RNA, SMALL INTERFERING; RNA-BINDING PROTEINS;

EID: 84872017252     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.2459     Document Type: Article

References (57)

1. Wang, Z. & Burge, C. B. Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA 14, 802-813 (2008).
2. Matlin, A. J., Clark, F. & Smith, C. W. Understanding alternative splicing: towards a cellular code. Nat. Rev. Mol. Cell Biol. 6, 386-398 (2005).
3. Blencowe, B. J. Alternative splicing: new insights from global analyses. Cell 126, 37-47 (2006).
4. Liu, H. X., Zhang, M. & Krainer, A. R. Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins. Genes Dev. 12, 1998-2012 (1998).
5. Fairbrother, W. G., Yeh, R. F., Sharp, P. A. & Burge, C. B. Predictive identification of exonic splicing enhancers in human genes. Science 297, 1007-1013 (2002).
6. Zhang, X. H. & Chasin, L. A. Computational definition of sequence motifs governing constitutive exon splicing. Genes Dev. 18, 1241-1250 (2004).
7. Wang, Z. et al. Systematic identification and analysis of exonic splicing silencers. Cell 119, 831-845 (2004).
8. Goren, A. et al. Comparative analysis identifies exonic splicing regulatory sequences-the complex definition of enhancers and silencers. Mol. Cell 22, 769-781 (2006).
9. Yu, Y. et al. Dynamic regulation of alternative splicing by silencers that modulate 5′ splice site competition. Cell 135, 1224-1236 (2008).
10. Culler, S. J., Hoff, K. G., Voelker, R. B., Berglund, J. A. & Smolke, C. D. Functional selection and systematic analysis of intronic splicing elements identifies active sequence motifs and associated splicing factors. Nucleic Acids Res. 38, 5152-5165 (2010).
11. Sharma, S., Kohlstaedt, L. A., Damianov, A., Rio, D. C. & Black, D. L. Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome. Nat. Struct. Mol. Biol. 15, 183-191 (2008).
12. Kashima, T., Rao, N. & Manley, J. L. An intronic element contributes to splicing repression in spinal muscular atrophy. Proc. Natl. Acad. Sci. USA 104, 3426-3431 (2007).
13. Hui, J. et al. Intronic CA-repeat and CA-rich elements: a new class of regulators of mammalian alternative splicing. EMBO J. 24, 1988-1998 (2005).
14. Blanchette, M. & Chabot, B. Modulation of exon skipping by high-affinity hnRNP A1-binding sites and by intron elements that repress splice site utilization. EMBO J. 18, 1939-1952 (1999).
15. Kanopka, A., Muhlemann, O. & Akusjarvi, G. Inhibition by SR proteins of splicing of a regulated adenovirus pre-mRNA. Nature 381, 535-538 (1996).
16. Ibrahim, E. C., Schaal, T. D., Hertel, K. J., Reed, R. & Maniatis, T. Serine/arginine-rich protein-dependent suppression of exon skipping by exonic splicing enhancers. Proc. Natl. Acad. Sci. USA 102, 5002-5007 (2005).
17. Shen, M. & Mattox, W. Activation and repression functions of an SR splicing regulator depend on exonic versus intronic-binding position. Nucleic Acids Res. 40, 428-437 (2012).
18. McNally, L. M. & McNally, M. T. SR protein splicing factors interact with the Rous sarcoma virus negative regulator of splicing element. J. Virol. 70, 1163-1172 (1996).
19. Del Gatto-Konczak, F., Olive, M., Gesnel, M. C. & Breathnach, R. hnRNP A1 recruited to an exon in vivo can function as an exon splicing silencer. Mol. Cell Biol. 19, 251-260 (1999).
20. Hua, Y., Vickers, T. A., Okunola, H. L., Bennett, C. F. & Krainer, A. R. Antisense masking of an hnRNP A1/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice. Am. J. Hum. Genet. 82, 834-848 (2008).
21. Tange, T. O., Damgaard, C. K., Guth, S., Valcarcel, J. & Kjems, J. The hnRNP A1 protein regulates HIV-1 tat splicing via a novel intron silencer element. EMBO J. 20, 5748-5758 (2001).
22. Wang, Y., Ma, M., Xiao, X. & Wang, Z. Intronic splicing enhancers, cognate splicing factors and context-dependent regulation rules. Nat. Struct. Mol. Biol. 19, 1044-1052 (2012).
23. Wang, Z., Xiao, X., Van Nostrand, E. & Burge, C. B. General and specific functions of exonic splicing silencers in splicing control. Mol. Cell 23, 61-70 (2006).
24. Lim, K. H., Ferraris, L., Filloux, M. E., Raphael, B. J. & Fairbrother, W. G. Using positional distribution to identify splicing elements and predict pre-mRNA processing defects in human genes. Proc. Natl. Acad. Sci. USA 108, 11093-11098 (2011).
25. Huang, C. et al. A structured RNA in HBV PRE represses alternative splicing in a sequence-independent and position-dependent manner. FEBS J. 278, 1533-1546 (2011).
26. Pervouchine, D. D. et al. Evidence for widespread association of mammalian splicing and conserved long-range RNA structures. RNA 18, 1-15 (2012).
27. Dominski, Z., Yang, X. C., Kaygun, H., Dadlez, M. & Marzluff, W. F. A 3′ exonuclease that specifically interacts with the 3′ end of histone mRNA. Mol. Cell 12, 295-305 (2003).
28. Rothrock, C. R., House, A. E. & Lynch, K. W. HnRNP L represses exon splicing via a regulated exonic splicing silencer. EMBO J. 24, 2792-2802 (2005).
29. Nielsen, F. C., Nielsen, J. & Christiansen, J. A family of IGF-II mRNA binding proteins (IMP) involved in RNA trafficking. Scand. J. Clin. Lab. Invest. Suppl. 234, 93-99 (2001).
30. Allemand, E., Hastings, M. L., Murray, M. V., Myers, M. P. & Krainer, A. R. Alternative splicing regulation by interaction of phosphatase PP2Cgamma with nucleic acid-binding protein YB-1. Nat. Struct. Mol. Biol. 14, 630-638 (2007).
31. Krainer, A. R., Conway, G. C. & Kozak, D. Purification and characterization of pre-mRNA splicing factor SF2 from HeLa cells. Genes Dev. 4, 1158-1171 (1990).
32. Muta, T., Kang, D., Kitajima, S., Fujiwara, T. & Hamasaki, N. p32 protein, a splicing factor 2-associated protein, is localized in mitochondrial matrix and is functionally important in maintaining oxidative phosphorylation. J. Biol. Chem. 272, 24363-24370 (1997).
33. Oberstrass, F. C. et al. Structure of PTB bound to RNA: specific binding and implications for splicing regulation. Science 309, 2054-2057 (2005).
34. Spellman, R., Llorian, M. & Smith, C. W. Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1. Mol. Cell 27, 420-434 (2007).
35. Jin, W., Bruno, I. G., Xie, T. X., Sanger, L. J. & Cote, G. J. Polypyrimidine tract-binding protein down-regulates fibroblast growth factor receptor 1 α-exon inclusion. Cancer Res. 63, 6154-6157 (2003).
36. Côté, J., Dupuis, S. & Wu, J. Y. Polypyrimidine track-binding protein binding downstream of caspase-2 alternative exon 9 represses its inclusion. J. Biol. Chem. 276, 8535-8543 (2001).
37. Das, R. et al. SR proteins function in coupling RNAP II transcription to pre-mRNA splicing. Mol. Cell 26, 867-881 (2007).
38. Chou, M. Y., Rooke, N., Turck, C. W. & Black, D. L. hnRNP H is a component of a splicing enhancer complex that activates a c-src alternative exon in neuronal cells. Mol. Cell Biol. 19, 69-77 (1999).
39. Kashima, T., Rao, N., David, C. J. & Manley, J. L. hnRNP A1 functions with specificity in repression of SMN2 exon 7 splicing. Hum. Mol. Genet. 16, 3149-3159 (2007).
40. Hui, J., Stangl, K., Lane, W. S. & Bindereif, A. HnRNP L stimulates splicing of the eNOS gene by binding to variable-length CA repeats. Nat. Struct. Biol. 10, 33-37 (2003).
41. Chen, M. & Manley, J. L. Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Nat. Rev. Mol. Cell Biol. 10, 741-754 (2009).
42. Graveley, B. R. & Maniatis, T. Arginine/serine-rich domains of SR proteins can function as activators of pre-mRNA splicing. Mol. Cell 1, 765-771 (1998).
43. Shen, H., Kan, J. L. & Green, M. R. Arginine-serine-rich domains bound at splicing enhancers contact the branchpoint to promote prespliceosome assembly. Mol. Cell 13, 367-376 (2004).
44. Graveley, B. R., Hertel, K. J. & Maniatis, T. A systematic analysis of the factors that determine the strength of pre-mRNA splicing enhancers. EMBO J. 17, 6747-6756 (1998).
45. Wang, Y., Cheong, C. G., Hall, T. M. & Wang, Z. Engineering splicing factors with designed specificities. Nat. Methods 6, 825-830 (2009).
46. Cheong, C. G. & Hall, T. M. Engineering RNA sequence specificity of Pumilio repeats. Proc. Natl. Acad. Sci. USA 103, 13635-13639 (2006).
47. Tourrière, H. et al. The RasGAP-associated endoribonuclease G3BP assembles stress granules. J. Cell Biol. 160, 823-831 (2003).
48. Ufer, C. et al. Translational regulation of glutathione peroxidase 4 expression through guanine-rich sequence-binding factor 1 is essential for embryonic brain development. Genes Dev. 22, 1838-1850 (2008).
49. Michlewski, G., Guil, S., Semple, C. A. & Caceres, J. F. Posttranscriptional regulation of miRNAs harboring conserved terminal loops. Mol. Cell 32, 383-393 (2008).
50. Guil, S., Long, J. C. & Caceres, J. F. hnRNP A1 relocalization to the stress granules reflects a role in the stress response. Mol. Cell Biol. 26, 5744-5758 (2006).
51. Boutz, P. L. et al. A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev. 21, 1636-1652 (2007).
52. Caputi, M. & Zahler, A. M. Determination of the RNA binding specificity of the heterogeneous nuclear ribonucleoprotein (hnRNP) H/H'/F/2H9 family. J. Biol. Chem. 276, 43850-43859 (2001).
53. Schaub, M. C., Lopez, S. R. & Caputi, M. Members of the heterogeneous nuclear ribonucleoprotein H family activate splicing of an HIV-1 splicing substrate by promoting formation of ATP-dependent spliceosomal complexes. J. Biol. Chem. 282, 13617-13626 (2007).
54. Chen, C. D., Kobayashi, R. & Helfman, D. M. Binding of hnRNP H to an exonic splicing silencer is involved in the regulation of alternative splicing of the rat beta-tropomyosin gene. Genes Dev. 13, 593-606 (1999).
55. Xiao, X., Wang, Z., Jang, M. & Burge, C. B. Coevolutionary networks of splicing cis-regulatory elements. Proc. Natl. Acad. Sci. USA 104, 18583-18588 (2007).
56. Xiao, X. et al. Splice site strength-dependent activity and genetic buffering by poly-G runs. Nat. Struct. Mol. Biol. 16, 1094-1100 (2009).
57. Katz, Y., Wang, E. T., Airoldi, E. M. & Burge, C. B. Analysis and design of RNA sequencing experiments for identifying isoform regulation. Nat. Methods 7, 1009-1015 (2010).