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

Global effects of the CSR-1 RNA interference pathway on the transcriptional landscape.
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DOI:
10.1038/nsmb.2801
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发表时间:
2014-04
影响因子:
16.8
通讯作者:
Grishok A
Grishok A
中科院分区:
生物学1区
文献类型:
--
作者:
Cecere G;Hoersch S;O'Keeffe S;Sachidanandam R;Grishok A

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已知ArgAerte蛋白及其小RNA辅助因子短干扰RNAs(SiRNAs)在转录和转录后水平上抑制基因表达。在秀丽隐杆线虫中,ArgAerte CSR-1与数千个内源siRNAs(Endo-siRNAs)结合在一起,反义到生殖系转录本,并以依赖于siRNA的方式与染色质结合。然而,它在基因表达调控中的作用仍然存在争议。在这里,我们使用了新生RNA转录本的全基因组图谱来证明CSR-1 RNAi途径促进面向正义的POL II转录。此外,CSR-1功能的丧失导致沉默染色质结构域的反义转录和异位转录的全球增加,从而导致着丝粒特异性组蛋白H3的染色质掺入减少。基于这些发现,我们认为CSR-1途径在维持活跃转录的方向性方面发挥了作用,从而传播了转录活跃和沉默基因组区域之间的区别。
Argonaute proteins and their small RNA co-factors short interfering RNAs (siRNAs) 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) antisense to germline transcripts and associates with chromatin in a siRNA-dependent manner. However, its role in gene expression regulation remains controversial. Here, we used a genome-wide profiling of nascent RNA transcripts to demonstrate that the CSR-1 RNAi pathway promotes sense-oriented Pol 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. Based on these findings, we propose that the CSR-1 pathway has a role in maintaining the directionality of active transcription thereby propagating the distinction between transcriptionally active and silent genomic regions.
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