Dicer-independent primal RNAs trigger RNAi and heterochromatin formation.

Dicer-independent primal RNAs trigger RNAi and heterochromatin formation.
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DOI:
10.1016/j.cell.2010.01.019
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发表时间:
2010-02-19
期刊:
影响因子:
64.5
通讯作者:
Moazed D
Moazed D
中科院分区:
生物学1区
文献类型:
--
作者:
Halic M;Moazed D

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裂殖酵母近着丝粒异染色质的组装和从非编码着丝粒转录物产生小干扰RNA(siRNA)是相互依赖的过程。这种相互依赖的正反馈循环最初是如何被触发的,这是一个根本的未解问题。在这里,我们表明,两个不同的Argonaute(Ago1)依赖性途径介导小RNA的产生。RNA依赖性RNA聚合酶复合物(RDRC)和Dicer作用于特定的非编码RNA,通过需要Ago1的切割活性但不依赖于预先存在的异染色质的机制产生siRNA。在没有RDRC或Dicer的情况下,一类独特的小RNA,称为原始小RNA(priRNAs),与Ago1相关。priRNA是大量转录物的降解产物,其结合Ago 1并靶向由DNA重复序列的双向转录产生的反义转录物。我们的研究结果表明,转录组监视机制的基础上随机协会的RNA降解产物Argonaute触发siRNA扩增和异染色质组装内的DNA重复。
Assembly of fission yeast pericentromeric heterochromatin and generation of small interfering RNAs (siRNAs) from noncoding centromeric transcripts are mutually dependent processes. How this interdependent positive feedback loop is first triggered is a fundamental unanswered question. Here, we show that two distinct Argonaute (Ago1)-dependent pathways mediate small RNA generation. RNA-dependent RNA polymerase complex (RDRC) and Dicer act on specific noncoding RNAs to generate siRNAs by a mechanism that requires the slicer activity of Ago1 but is independent of pre-existing heterochromatin. In the absence of RDRC or Dicer, a distinct class of small RNAs, called primal small RNAs (priRNAs), associates with Ago1. priRNAs are degradation products of abundant transcripts, which bind to Ago1 and target antisense transcripts that result from bidirectional transcription of DNA repeats. Our results suggest that a transcriptome surveillance mechanism based on random association of RNA degradation products with Argonaute triggers siRNA amplification and heterochromatin assembly within DNA repeats.
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