U2AF65 adapts to diverse pre-mRNA splice sites through conformational selection of specific and promiscuous RNA recognition motifs

Nucleic Acids Research

Volumn 41, Issue 6, 2013, Pages 3859-3873

  Jenkins, Jermaine L ^a   Agrawal, Anant A ^a   Gupta, Ankit ^a   Green, Michael R ^b   Kielkopf, Clara L ^a  

^a UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^b UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING PROTEIN; CYTIDINE; CYTOSINE; DEOXYRIBOSE; DEOXYURIDINE; MESSENGER RNA PRECURSOR; PROTEIN U2AF65; PYRIMIDINE; UNCLASSIFIED DRUG; URACIL; MESSENGER RNA; NUCLEAR PROTEIN; PYRIMIDINE DERIVATIVE; RIBONUCLEOPROTEIN; RNA PRECURSOR; SPLICING FACTOR U2AF; URIDINE;

ARTICLE; CRYSTAL STRUCTURE; CRYSTALLIZATION; MUTANT; PRIORITY JOURNAL; PROTEIN MOTIF; RNA CONFORMATION; RNA SPLICING; WILD TYPE; CHEMICAL STRUCTURE; CHEMISTRY; HUMAN; METABOLISM; PROTEIN BINDING;

EUKARYOTA;

AMINO ACID MOTIFS; CYTIDINE; HUMANS; MODELS, MOLECULAR; NUCLEAR PROTEINS; PROTEIN BINDING; PYRIMIDINES; RIBONUCLEOPROTEINS; RNA PRECURSORS; RNA SPLICE SITES; RNA, MESSENGER; URIDINE;

MLCS; MLOWN;

EID: 84876046010     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkt046     Document Type: Article

References (43)

1. Wang, E.T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S.F., Schroth, G.P. and Burge, C.B. (2008) Alternative isoform regulation in human tissue transcriptomes. Nature, 456, 470-476.
2. Smith, D.J., Query, C.C. and Konarska, M.M. (2008) "Nought may endure but mutability'': spliceosome dynamics and the regulation of splicing. Mol. Cell, 30, 657-666.
3. Itoh, H., Washio,T. and Tomita, M. (2004) Computational comparative analyses of alternative splicing regulation using full-length cDNA of various eukaryotes. RNA, 10, 1005-1018.
4. Senapathy, P., Shapiro, M.B. and Harris, N.L. (1990) Splice junctions, branch point sites, and exons: sequence statistics, identification, and applications to genome project. Methods Enzymol., 183, 252-278.
5. Irimia,M. and Roy, S.W. (2008) Evolutionary convergence on highly-conserved 3′ intron structures in intron-poor eukaryotes and insights into the ancestral eukaryotic genome. PLoS Genet., 4, e1000148.
6. Bouck, J., Litwin, S., Skalka, A.M. and Katz, R.A. (1998) In vivo selection for intronic splicing signals from a randomized pool. Nucleic Acids Res., 26, 4516-4523.
7. Coolidge, C.J., Seely, R.J. and Patton, J.G. (1997) Functional analysis of the polypyrimidine tract in pre-mRNA splicing. Nucleic Acids Res., 25, 888-896.
8. Ruskin,B. and Green, M.R. (1985) Role of the 3′ splice site consensus sequence in mammalian pre-mRNA splicing. Nature, 317, 732-734.
9. Roscigno, R.F., Weiner,M. and Garcia-Blanco, M.A. (1993) A mutational analysis of the polypyrimidine tract of introns. Effects of sequence differences in pyrimidine tracts on splicing. J. Biol. Chem., 268, 11222-11229.
10. Baralle, D., Lucassen,A. and Buratti, E. (2009) Missed threads. The impact of pre-mRNA splicing defects on clinical practice. EMBO Rep., 10, 810-816.
11. David, C.J. and Manley, J.L. (2010) Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged. Genes Dev., 24, 2343-2364.
12. Chu, C.S., Trapnell, B.C., Curristin, S., Cutting, G.R. and Crystal, R.G. (1993) Genetic basis of variable exon 9 skipping in cystic fibrosis transmembrane conductance regulator mRNA. Nat. Genet., 3, 151-156.
13. Chillon, M., Casals, T., Mercier, B., Bassas, L., Lissens, W., Silber, S., Romey, M.C., Ruiz-Romero, J., Verlingue, C., Claustres, M. et al. (1995) Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N. Engl. J. Med., 332, 1475-1480.
14. Ruskin, B., Zamore, P.D. and Green, M.R. (1988) A factor, U2AF, is required for U2 snRNP binding and splicing complex assembly. Cell, 52, 207-219.
15. Zamore, P.D. and Green, M.R. (1989) Identification, purification, and biochemical characterization of U2 small nuclear ribonucleoprotein auxiliary factor. Proc. Natl Acad. Sci. USA, 86, 9243-9247.
16. Zamore, P.D. and Green, M.R. (1991) Biochemical characterization of U2 snRNP auxiliary factor: an essential pre-mRNA splicing factor with a novel intranuclear distribution. EMBO J., 10, 207-214.
17. Zamore, P.D., Patton, J.G. and Green, M.R. (1992) Cloning and domain structure of the mammalian splicing factor U2AF. Nature, 355, 609-614.
18. Golling, G., Amsterdam, A., Sun, Z., Antonelli, M., Maldonado, E., Chen, W., Burgess, S., Haldi, M., Artzt, K., Farrington, S. et al. (2002) Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development. Nat. Genet., 31, 135-140.
19. Zuccato, E., Buratti, E., Stuani, C., Baralle, F.E. and Pagani, F. (2004) An intronic polypyrimidine-rich element downstream of the donor site modulates cystic fibrosis transmembrane conductance regulator exon 9 alternative splicing. J. Biol. Chem., 279, 16980-16988.
20. Tiscornia,G. and Mahadevan, M.S. (2000) Myotonic dystrophy: the role of the CUG triplet repeats in splicing of a novel DMPK exon and altered cytoplasmic DMPK mRNA isoform ratios. Mol. Cell, 5, 959-967.
21. Davies, R.C., Calvio, C., Bratt, E., Larsson, S.H., Lamond, A.I. and Hastie, N.D. (1998) WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes. Genes Dev., 12, 3217-3225.
22. Fay, J., Kelehan, P., Lambkin,H. and Schwartz, S. (2009) Increased expression of cellular RNA-binding proteins in HPV-induced neoplasia and cervical cancer. J. Med. Virol., 81, 897-907.
23. Chen, Y., Zhang,L. and Jones, K.A. (2011) SKIP counteracts p53-mediated apoptosis via selective regulation of p21Cip1 mRNA splicing. Genes Dev., 25, 701-716.
24. Banerjee, H., Rahn, A., Gawande, B., Guth, S., Valcarcel,J. and Singh, R. (2004) The conserved RNA recognition motif 3 of U2 snRNA auxiliary factor (U2AF65) is essential in vivo but dispensable for activity in vitro. RNA, 10, 240-253.
25. Sickmier, E.A., Frato, K.E., Shen, H., Paranawithana, S.R., Green, M.R. and Kielkopf, C.L. (2006) Structural basis of polypyrimidine tract recognition by the essential pre-mRNA splicing factor, U2AF65. Mol. Cell, 23, 49-59.
26. Mackereth, C.D., Madl, T., Bonnal, S., Simon, B., Zanier, K., Gasch, A., Rybin, V., Valcarcel,J. and Sattler, M. (2011) Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF. Nature, 475, 408-411.
27. Sickmier, E.A., Frato, K.E. and Kielkopf, C.L. (2006) Crystallization and preliminary X-ray analysis of U2AF65 variant in complex with a polypyrimidine tract analogue by use of protein engineering. Acta Crystallogr, F62, 457-459.
28. Singh, R., Banerjee,H. and Green, M.R. (2000) Differential recognition of the polypyrimidine-tract by the general splicing factor U2AF65 and the splicing repressor Sex-lethal. RNA, 6, 901-911.
29. Jenkins, J.L., Shen, H., Green, M.R. and Kielkopf, C.L. (2008) Solution conformation and thermodynamic characteristics of RNA binding by the splicing factor U2AF65. J. Biol. Chem., 283, 33641-33649.
30. Vagin, A.A., Steiner, R.A., Lebedev, A.A., Potterton, L., McNicholas, S., Long,F. and Murshudov, G.N. (2004) REFMAC5 dictionary: organization of prior chemical knowledge and guidelines for its use. Acta Crystallogr., D60, 2184-2195.
31. Myers, J.K., Pace, C.N. and Scholtz, J.M. (1995) Denaturant m values and heat capacity changes: relation to changes in accessible surface areas of protein unfolding. Protein Sci., 4, 2138-2148.
32. Cavaluzzi, M.J. and Borer, P.N. (2004) Revised UV extinction coefficients for nucleoside-5′-monophosphates and unpaired DNA and RNA. Nucleic Acids Res., 32, e13.
33. Bernado, P., Mylonas, E., Petoukhov, M.V., Blackledge,M. and Svergun, D.I. (2007) Structural characterization of flexible proteins using small-angle X-ray scattering. J. Am. Chem. Soc., 129, 5656-5664.
34. Sternglanz,H. and Bugg, C.E. (1975) Relationship between the mutagenic and base-stacking properties of halogenated uracil derivatives. The crystal structures of 5-chloro-and 5-bromouracil. Biochim. Biophys. Acta, 378, 1-11.
35. Thickman, K.R., Sickmier, E.A. and Kielkopf, C.L. (2007) Alternative conformations at the RNA-binding surface of the N-terminal U2AF65 RNA recognition motif. J. Mol. Biol., 366, 703-710.
36. Clery, A., Blatter,M. and Allain, F.H. (2008) RNA recognition motifs: boring? Not quite. Curr. Opin. Struct. Biol., 18, 290-298.
37. Jenkins, J.L., Laird, K.M. and Kielkopf, C.L. (2012) A broad range of conformations contribute to the solution ensemble of the essential splicing factor U2AF65. Biochemistry, 51, 5223-5225.
38. Gupta, A., Jenkins, J.L. and Kielkopf, C.L. (2010) RNA induces conformational changes in the SF1-U2AF65 splicing factor complex. J. Mol. Biol., 405, 1128-1138.
39. Rain, J.C., Rafi, Z., Rhani, Z., Legrain,P. and Kramer, A. (1998) Conservation of functional domains involved in RNA binding and protein-protein interactions in human and Saccharomyces cerevisiae pre-mRNA splicing factor SF1. RNA, 4, 551-565.
40. Banerjee, H., Rahn, A., Davis,W. and Singh, R. (2003) Sex lethal and U2 small nuclear ribonucleoprotein auxiliary factor (U2AF65) recognize polypyrimidine tracts using multiple modes of binding. RNA, 9, 88-99.
41. Hollins, C., Zorio, D.A., MacMorris,M. and Blumenthal, T. (2005) U2AF binding selects for the high conservation of the C. elegans 3′ splice site. RNA, 11, 248-253.
42. Patterson,B. and Guthrie, C. (1991) A U-rich tract enhances usage of an alternative 3′ splice site in yeast. Cell, 64, 181-187.
43. Davis, I.W., Murray, L.W., Richardson, J.S. and Richardson, D.C. (2004) MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes. Nucleic Acids Res., 32, W615-W619.