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Global effects of the CSR-1 RNA interference pathway on the transcriptional landscape.


ABSTRACT: Argonaute proteins and their small RNA cofactors short interfering RNAs are known to inhibit gene expression at the transcriptional and post-transcriptional levels. In Caenorhabditis elegans, the Argonaute CSR-1 binds thousands of endogenous siRNAs (endo-siRNAs) that are antisense to germline transcripts. However, its role in gene expression regulation remains controversial. Here we used genome-wide profiling of nascent RNA transcripts and found that the CSR-1 RNA interference pathway promoted sense-oriented RNA polymerase II transcription. Moreover, a loss of CSR-1 function resulted in global increase in antisense transcription and ectopic transcription of silent chromatin domains, which led to reduced chromatin incorporation of centromere-specific histone H3. On the basis of these findings, we propose that the CSR-1 pathway helps maintain the directionality of active transcription, thereby propagating the distinction between transcriptionally active and silent genomic regions.

SUBMITTER: Cecere G 

PROVIDER: S-EPMC4068146 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Global effects of the CSR-1 RNA interference pathway on the transcriptional landscape.

Cecere Germano G   Hoersch Sebastian S   O'Keeffe Sean S   Sachidanandam Ravi R   Grishok Alla A  

Nature structural & molecular biology 20140330 4


Argonaute proteins and their small RNA cofactors short interfering RNAs are known to inhibit gene expression at the transcriptional and post-transcriptional levels. In Caenorhabditis elegans, the Argonaute CSR-1 binds thousands of endogenous siRNAs (endo-siRNAs) that are antisense to germline transcripts. However, its role in gene expression regulation remains controversial. Here we used genome-wide profiling of nascent RNA transcripts and found that the CSR-1 RNA interference pathway promoted s  ...[more]

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