期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 16, 期 7, 页码 717-U43出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1620
关键词
-
资金
- Fundacion Antorchas
- Agencia Nacional de Promocion de Ciencia y Tecnologia of Argentina
- University of Buenos Aires
- European Alternative Splicing Network
- Genome Canada
- Genome Quebec
- Consejo Nacional de Investigaciones Cientificas y Tecnicas of Argentina
- Howard Hughes Medical Institute
- ICREA Funding Source: Custom
When targeting promoter regions, small interfering RNAs (siRNAs) trigger a previously proposed pathway known as transcriptional gene silencing by promoting heterochromatin formation. Here we show that siRNAs targeting intronic or exonic sequences close to an alternative exon regulate the splicing of that exon. The effect occurred in hepatoma and HeLa cells with siRNA antisense strands designed to enter the silencing pathway, suggesting hybridization with nascent pre-mRNA. Unexpectedly, in HeLa cells the sense strands were also effective, suggesting that an endogenous antisense transcript, detectable in HeLa but not in hepatoma cells, acts as a target. The effect depends on Argonaute-1 and is counterbalanced by factors favoring chromatin opening or transcriptional elongation. The increase in heterochromatin marks (dimethylation at Lys9 and trimethylation at Lys27 of histone H3) at the target site, the need for the heterochromatin-associated protein HP1 alpha and the reduction in RNA polymerase II processivity suggest a mechanism involving the kinetic coupling of transcription and alternative splicing.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据