期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 16, 期 10, 页码 1094-U119出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1661
关键词
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资金
- American Heart Association
- Human Frontiers Science Program
- US National Institutes of Health (NIH)
- US National Science Foundation (NSF) [DBI-0821391]
Pre-mRNA splicing is regulated through the combinatorial activity of RNA motifs, including splice sites and splicing regulatory elements. Here we show that the activity of the G-run (polyguanine sequence) class of splicing enhancer elements is similar to 4-fold higher when adjacent to intermediate strength 5' splice sites ( ss) than when adjacent to weak 5' ss, and similar to 1.3-fold higher relative to strong 5' ss. We observed this dependence on 5' ss strength in both splicing reporters and in global microarray and mRNA-Seq analyses of splicing changes following RNA interference against heterogeneous nuclear ribonucleoprotein ( hnRNP) H, which cross-linked to G-runs adjacent to many regulated exons. An exon's responsiveness to changes in hnRNP H levels therefore depends in a complex way on G-run abundance and 5' ss strength. This pattern of activity enables G-runs and hnRNP H to buffer the effects of 5' ss mutations, augmenting both the frequency of 5' ss polymorphism and the evolution of new splicing patterns. Certain other splicing factors may function similarly.
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