期刊
GENES & DEVELOPMENT
卷 27, 期 2, 页码 129-144出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.209759.112
关键词
splicing; U1 snRNA; pre-mRNA; 5 ' splice sites; exons
资金
- Biotechnology and Biological Sciences Research Council [BBS/B/0367X] Funding Source: Medline
- NIGMS NIH HHS [R37 GM042699, R01 GM042699] Funding Source: Medline
- Biotechnology and Biological Sciences Research Council [BBS/B/0367X] Funding Source: researchfish
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.
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