Human Molecular Genetics Advance Access published online on April 27, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi164
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel
* To whom correspondence should be addressed. The formation of base-pairing between the branch-site sequence and U2 snRNP is an important step in mRNA splicing. We developed a new algorithm to identify both the branch-site sequence and the polypyrimidine tract, and validated its predictions experimentally. To assess the branch-site conservation between human and mouse, we assembled and analyzed 46,812 and 242 constitutively and alternatively spliced orthologs human-mouse intron pairs, respectively. Combinations of branch-sites and polypyrimidine tracts can be found in most of the constitutive and alternative introns. An average distance between the branch-site and the 3' splice site is 33-34 nucleotides. Acceptor-like AG dinucleotides that resided between the predicted branch-site and the 3' splice site were found to appear mostly within 5 nucleotides, but not more than 19 nucleotides, downstream of the branch-site. However, while 32% of homologous alternatively spliced branch-site sequences were fully conserved between human and mouse, only a small fraction (3%) of homologous constitutively counterparts were fully conserved. This indicates that the full sequence of the branch-site is under weak purifying selection in constitutively spliced introns and, further, strengthens the view that branch-site sequence is just one of several factors determining the ability of the splicing machinery to identify the branch-site location. Mutations in the putative branch-site revealed a shift from constitutive to alternative splicing, and it also controls the inclusion/skipping ratio in alternative splicing. This suggests a role for branch-site sequence in regulated splicing.
Received February 3, 2005
Revised March 27, 2005
Accepted April 13, 2005
Article
Human-Mouse Comparative Analysis reveals that Branch-site plasticity contributes to splicing regulation
Gil Ast, E-mail: gilast{at}post.tau.ac.il
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Schwartz, E. Hall, and G. Ast SROOGLE: webserver for integrative, user-friendly visualization of splicing signals Nucleic Acids Res., July 1, 2009; 37(suppl_2): W189 - W192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-O. Desmet, D. Hamroun, M. Lalande, G. Collod-Beroud, M. Claustres, and C. Beroud Human Splicing Finder: an online bioinformatics tool to predict splicing signals Nucleic Acids Res., May 1, 2009; 37(9): e67 - e67. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Friedman, M. B. Stadler, N. Shomron, Y. Ding, and C. B. Burge Ab initio identification of functionally interacting pairs of cis-regulatory elements Genome Res., October 1, 2008; 18(10): 1643 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Wang and C. B. Burge Splicing regulation: From a parts list of regulatory elements to an integrated splicing code RNA, May 1, 2008; 14(5): 802 - 813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Gal-Mark, S. Schwartz, and G. Ast Alternative splicing of Alu exons--two arms are better than one Nucleic Acids Res., April 1, 2008; 36(6): 2012 - 2023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Gao, A. Masuda, T. Matsuura, and K. Ohno Human branch point consensus sequence is yUnAy Nucleic Acids Res., April 1, 2008; 36(7): 2257 - 2267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Schwartz, J. Silva, D. Burstein, T. Pupko, E. Eyras, and G. Ast Large-scale comparative analysis of splicing signals and their corresponding splicing factors in eukaryotes Genome Res., January 1, 2008; 18(1): 88 - 103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Akerman and Y. Mandel-Gutfreund Does distance matter? Variations in alternative 3' splicing regulation Nucleic Acids Res., August 17, 2007; (2007) gkm603v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-W. Tsai, W.-Y. Tarn, and W.-c. Lin Wobble Splicing Reveals the Role of the Branch Point Sequence-to-NAGNAG Region in 3' Tandem Splice Site Selection Mol. Cell. Biol., August 15, 2007; 27(16): 5835 - 5848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xia, J. Bi, and Y. Li Identification of alternative 5'/3' splice sites based on the mechanism of splice site competition Nucleic Acids Res., December 4, 2006; 34(21): 6305 - 6313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Vorechovsky Aberrant 3' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization Nucleic Acids Res., September 15, 2006; (2006) gkl535v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xing, Q. Wang, and C. Lee Evolutionary Divergence of Exon Flanks: A Dissection of Mutability and Selection Genetics, July 1, 2006; 173(3): 1787 - 1791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kralovicova and I. Vorechovsky Position-Dependent Repression and Promotion of DQB1 Intron 3 Splicing by GGGG Motifs J. Immunol., February 15, 2006; 176(4): 2381 - 2388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kralovicova, M. B. Christensen, and I. Vorechovsky Biased exon/intron distribution of cryptic and de novo 3' splice sites Nucleic Acids Res., September 1, 2005; 33(15): 4882 - 4898. [Abstract] [Full Text] [PDF]
|
|