期刊
MOLECULAR CELL
卷 45, 期 5, 页码 656-668出版社
CELL PRESS
DOI: 10.1016/j.molcel.2012.01.009
关键词
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资金
- China 863 program [2007AA02Z112]
- NSFC [30770422]
- China 973 program [2005CB724604]
- Chinese 111 project [B06018]
- NIH [HG004659, GM049369, GM052872]
The nuclear matrix-associated hnRNP U/SAF-A protein has been implicated in diverse pathways from transcriptional regulation to telomere length control to X inactivation, but the precise mechanism underlying each of these processes has remained elusive. Here, we report hnRNP U as a regulator of SMN2 splicing from a custom RNAi screen. Genome-wide analysis by CLIP-seq reveals that hnRNP U binds virtually to all classes of regulatory noncoding RNAs, including all snRNAs required for splicing of both major and minor classes of introns, leading to the discovery that hnRNP U regulates U2 snRNP maturation and Cajal body morphology in the nucleus. Global analysis of hnRNP U-dependent splicing by RNA-seq coupled with bioinformatic analysis of associated splicing signals suggests a general rule for splice site selection through modulating the core splicing machinery. These findings exemplify hnRNP U/SAF-A as a potent regulator of nuclear ribonucleoprotein particles in diverse gene expression pathways.
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