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Humanmouse comparative analysis reveals that branch-site plasticity contributes to

Summary: Human­mouse comparative analysis reveals
that branch-site plasticity contributes to
splicing regulation
Guy Kol, Galit Lev-Maor and Gil Ast*
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University,
Ramat Aviv 69978, Tel Aviv, Israel
Received February 3, 2005; Revised March 27, 2005; Accepted April 13, 2005
The formation of base-pairing between the branch-site (BS) sequence and the U2 snRNP is an important step
in mRNA splicing. We developed a new algorithm to identify both the BS sequence and the polypyrimidine
tract (PPT) and validated its predictions experimentally. To assess BS conservation between human and
mouse, we assembled and analyzed 46 812 and 242 constitutively and alternatively spliced orthologs of
human­mouse intron pairs, respectively. Combinations of BSs and PPTs can be found in most of the
constitutive and alternative introns. The average distance between the BS and the 30
splice site (30
ss) is
33­34 nt. Acceptor-like AG dinucleotides that resided between the predicted BS and the 30
ss were found
to appear mostly within 5 nt, but not more than 19 nt, downstream of the BS. However, although 32% of
homologous alternatively spliced BS sequences were fully conserved between human and mouse, only a
small fraction (3%) of homologous constitutive counterparts was fully conserved. This indicates that the


Source: Ast, Gil - Department of Molecular Genetics and Biochemistry, Tel Aviv University


Collections: Biology and Medicine