RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing
RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing
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DOI：
10.1038/ng1452
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发表时间：
2004-11-01
期刊：
影响因子：
30.8
通讯作者：
Grewal, SIS
中科院分区：
文献类型：
--
作者：
Noma, K;Sugiyama, T;Grewal, SIS
RNA干扰是一种保守的机制，通过双链RNA加工成短干扰RNA (sirna)，可以触发转录后和转录基因沉默。在裂变酵母中，rna诱导的转录基因沉默起始（RITS）复合体含有dicer生成的sirna，是异色沉默所必需的。在这里，我们发现BITS成分，包括Argonaute蛋白，结合到所有已知的异染色质位点。在配对型区域，BITS以Dicer依赖的方式被招募到着丝粒同源重复序列cenH中，而BITS在整个20 kb沉默区域的扩散及其随后的维持，需要包括Swi6在内的异染色质机制，即使在没有Dicer的情况下也会发生。此外，我们的分析表明，RNA干扰机制在顺式中作为异色结构域的稳定组成部分起作用，BITS在Lys9位点通过组蛋白H3的甲基化连接到沉默位点。这种捆绑促进转录本的加工和产生额外的sirna来维持异染色质。
RNA interference is a conserved mechanism by which double-stranded RNA is processed into short interfering RNAs (siRNAs) that can trigger both post-transcriptional and transcriptional gene silencing. In fission yeast, the RNA-induced initiation of transcriptional gene silencing (RITS) complex contains Dicer-generated siRNAs and is required for heterochromatic silencing. Here we show that BITS components, including Argonaute protein, bind to all known heterochromatic loci. At the mating-type region, BITS is recruited to the centromere-homologous repeat cenH in a Dicer-dependent manner, whereas the spreading of BITS across the entire 20-kb silenced domain, as well as its subsequent maintenance, requires heterochromatin machinery including Swi6 and occurs even in the absence of Dicer. Furthermore, our analyses suggest that RNA interference machinery operates in cis as a stable component of heterochromatic domains with BITS tethered to silenced loci by methylation of histone H3 at Lys9. This tethering promotes the processing of transcripts and generation of additional siRNAs for heterochromatin maintenance.