Pick one, but be quick : 5' splice sites and the problems of too many choices
Krainer, Adrian R.
Eperon, Ian C.
Date of Issue2013
School of Biological Sciences
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.
Genes & development
© 2013 The Author(s). This paper was published in Genes & Development and is made available as an electronic reprint (preprint) with permission of The Author(s). The paper can be found at the following official DOI: [http://dx.doi.org/10.1101/gad.209759.112]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.