RNAi-dependent and -independent RNA turnover mechanisms contribute to heterochromatic gene silencing
RNAi-dependent and -independent RNA turnover mechanisms contribute to heterochromatic gene silencing
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DOI：
10.1016/j.cell.2007.03.038
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发表时间：
2007-05-18
期刊：
影响因子：
64.5
通讯作者：
Moazed, Danesh
中科院分区：
文献类型：
--
作者：
Buehler, Marc;Haas, Wilhelm;Moazed, Danesh
在分裂酵母中，RNAi途径是依赖异染色质沉默着丝粒重复序列上的转基因插入所必需的，并与其他途径一起作用于沉默交配型基因座上的转基因。在这里，我们证明了着丝粒重复序列上的转基因转录产物被加工成siRNAs，因此是RNAL的直接靶标。此外，我们还证明了Cid14，聚(A)聚合酶Trf4/5家族的成员，具有异色基因沉默所必需的聚(A)聚合酶活性。令人惊讶的是，虽然CID14 Delta细胞中的siRNA水平显著降低，但异染色质的结构完整性似乎得到了保护。Cid14位于一个类似于在发芽酵母中发现的TRAMP复合体中的复合体中，这是降解异常转录的核监测机制的一部分。我们的发现表明，通过外切体和/或RNAi机制的招募，由TraMP样复合体进行的多聚腺苷基化有助于在分裂酵母中强大地沉默异色基因。
In fission yeast, the RNAi pathway is required for heterochromatin-dependent silencing of transgene insertions at centromeric repeats and acts together with other pathways to silence transgenes at the silent mating-type locus. Here, we show that transgene transcripts at centromeric repeats are processed into siRNAs and are therefore direct targets of RNAL Furthermore, we show that Cid14, a member of the Trf4/5 family of poly(A) polymerases, has poly(A) polymerase activity that is required for heterochromatic gene silencing. Surprisingly, while siRNA levels in cid14 Delta cells are dramatically reduced, the structural integrity of heterochromatin appears to be preserved. Cid14 resides in a complex similar to the TRAMP complex found in budding yeast, which is part of a nuclear surveillance mechanism that degrades aberrant transcripts. Our findings indicate that polyadenylation by a TRAMP-like complex contributes to robust silencing of heterochromatic genes in fission yeast via the recruitment of the exosome and/or the RNAi machinery.