Pick one, but be quick: 5' splice sites and the problems of too many choices.
Splice site selection is fundamental to pre-mRNA splicing and the expansion of genomic coding potential. 5' Splice sites (5'ss) are the critical elements at the 5' end of introns and are extremely diverse, as thousands of different sequences act as bona fide 5'ss in the human transcriptome. Most 5'ss are recognized by base-pairing with the 5' end of the U1 small nuclear RNA (snRNA). Here we review the history of research on 5'ss selection, highlighting the difficulties of establishing how base-pairing strength determines splicing outcomes. We also discuss recent work demonstrating that U1 snRNA:5'ss helices can accommodate noncanonical registers such as bulged duplexes. In addition, we describe the mechanisms by which other snRNAs, regulatory proteins, splicing enhancers, and the relative positions of alternative 5'ss contribute to selection. Moreover, we discuss mechanisms by which the recognition of numerous candidate 5'ss might lead to selection of a single 5'ss and propose that protein complexes propagate along the exon, thereby changing its physical behavior so as to affect 5'ss selection.
School of Biological Sciences, Division of Molecular Genetics and Cell Biology, Nanyang Technological University, Singapore. xroca@ntu.edu.sg
Xavier
X
Roca
Adrian R
AR
Krainer
Ian C
IC
Eperon
D017398:Alternative Splicing; D000818:Animals; D020029:Base Pairing; D004277:DNA, Single-Stranded / Q000378:metabolism; D030342:Genetic Diseases, Inborn / Q000235:genetics; D006801:Humans; D022821:RNA Splice Sites / Q000235:genetics*; D012326:RNA Splicing; D012342:RNA, Small Nuclear / Q000235:genetics
D004277:DNA, Single-Stranded; D022821:RNA Splice Sites; D012342:RNA, Small Nuclear; C405483:U1 small nuclear RNA