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U2AF binding selects for the high conservation of the C elegans 3 splice site
U2AF binding selects for the high conservation of the C. elegans 3' splice site.
89
Caenorhabditis elegans is unusual among animals in having a highly conserved octamer sequence at the 3' splice site: UUUU CAG/R. This sequence can bind to the essential heterodimeric splicing factor U2AF, with U2AF65 contacting the U tract and U2AF35 contacting the splice site itself (AG/R). Here we demonstrate a strong correspondence between binding to U2AF of RNA oligonucleotides with variant octamer sequences and the frequency with which such variations occur in splice sites. C. elegans U2AF has a strong preference for the octamer sequence and exerts much of the pressure for 3' splice sites to have the precise UUUUCAG/R sequence. At two positions the splice site has a very strong preference for U even though alternative bases can also bind tightly to U2AF, suggesting that evolution can select against sequences that may have a relatively modest reduction in binding. Although pyrimidines are frequently present at the first base in the exon, U2AF has a very strong bias against them, arguing there is a mechanism to compensate for weakened U2AF binding at this position. Finally, the C in the consensus sequence must remain adjacent to the AG/R rather than to the stretch of U's, suggesting this C is recognized by U2AF35.
Hollins C, Zorio DA, MacMorris M, Blumenthal T
RNA (New York, N.Y.)
2005-03-01 00:00
11
3
248-53
Animals,Animals, Genetically Modified,Caenorhabditis elegans,Nuclear Proteins,Precipitin Tests,Protein Binding,RNA Splicing,Ribonucleoproteins,Nuclear Proteins,Ribonucleoproteins,splicing factor U2AF
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Mail Stop 8101, PO Box 6511, Aurora, CO 80045, USA
RNA
NIGMS R01 GM59027
1355-8382
10.1261/rna.7221605
rna.7221605
79
True
15661845
