Argonaute slicing is required for heterochromatic silencing and spreading

Argonaute slicing is required for heterochromatic silencing and spreading
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DOI:
10.1126/science.1128813
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发表时间:
2006-08-25
期刊:
影响因子:
56.9
通讯作者:
Martienssen, Robert A.
Martienssen, Robert A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Irvine, Danielle V.;Zaratiegui, Mikel;Martienssen, Robert A.

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小干扰RNA(siRNA)通过Argonaute和RNA依赖的RNA聚合酶复合物,以及与RNA或DNA的碱基配对,引导组蛋白H3赖氨酸 - 9(H3K9me2)的二甲基化。我们发现Argonaute在异染色质沉默以及对与siRNA互补的靶标信使进行类似核糖核酸酶H的切割(剪切)时,需要保守的天冬氨酸 - 天冬氨酸 - 组氨酸基序。在裂殖酵母粟酒裂殖酵母中,异染色质重复序列由聚合酶II转录。我们表明当沉默报告基因嵌入这些转录本中时,H3K9me2会扩散到其中,并且这种扩散需要通读转录以及Argonaute的剪切。因此,siRNA通过与RNA的碱基配对相互作用引导组蛋白修饰。
Small interfering RNA ( siRNA) guides dimethylation of histone H3 lysine-9 (H3K9me2) via the Argonaute and RNA-dependent RNA polymerase complexes, as well as base-pairing with either RNA or DNA. We show that Argonaute requires the conserved aspartate-aspartate-histidine motif for heterochromatic silencing and for ribonuclease H - like cleavage ( slicing) of target messages complementary to siRNA. In the fission yeast Schizosaccharomyces pombe, heterochromatic repeats are transcribed by polymerase II. We show that H3K9me2 spreads into silent reporter genes when they are embedded within these transcripts and that spreading requires read-through transcription, as well as slicing by Argonaute. Thus, siRNA guides histone modification by base-pairing interactions with RNA.