Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 16, Issue 10, Pages 1094-U119Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1661
Keywords
-
Funding
- American Heart Association
- Human Frontiers Science Program
- US National Institutes of Health (NIH)
- US National Science Foundation (NSF) [DBI-0821391]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available