Post-transcriptional regulation of meiotic genes by a nuclear RNA silencing complex.
Post-transcriptional regulation of meiotic genes by a nuclear RNA silencing complex.
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DOI：
10.1261/rna.044479.114
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发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Moazed D
中科院分区：
文献类型：
--
作者：
Egan ED;Braun CR;Gygi SP;Moazed D
作者定义了一种多蛋白核RNA沉默(NOS)复合体，它介导了分裂酵母S.pombe营养生长过程中减数分裂基因的沉默。减数分裂基因沉默发生在转录后，通过招募外切体复合体来促进RNA降解。广泛的相互作用分析和功能表征将NERS复合体与特定的RNA结合和加工蛋白以及染色质修饰机制联系起来。RNA是调节多种细胞过程的基因沉默途径的核心组成部分。在裂殖酵母中，一种基于RNA的机制抑制营养生长过程中的减数分裂基因表达。这一途径依赖于锌指蛋白Red1，它是降解减数分裂mRNAs和靶向组蛋白H3赖氨酸9(H3K9)甲基化所必需的，组蛋白H3赖氨酸9(H3K9)甲基化是一种抑制染色质的标记，是减数分裂基因的子集。然而，Red1功能的机制尚不清楚。在这里，我们使用亲和纯化和质谱分析来鉴定一个含有Red1的核RNA沉默(NOS)复合体。除了Red1，这个复合体还包括Mtl1、Red5、Ars2、Rmn1和Iss10蛋白，并与其他几个参与信号或介导RNA沉默的复合体有关。通过分析基因敲除和可诱导的敲除等位基因的影响，我们发现NERS亚基在减数分裂基因上调节RNA降解和H3K9甲基化。我们还确定了单个nos亚基在与Mmi1和核外体RNA降解复合体相互作用中的作用。Mmi1是一种RNA结合蛋白，标志着减数分裂RNA的破坏。最后，我们发现，减数分裂基因上的H3K9甲基化水平不足以限制RNA聚合酶II的访问或抑制营养生长过程中的基因表达。我们的结果表明，Red1与其他蛋白质合作，在转录后水平上抑制减数分裂基因的表达。人类细胞中NORS样复合体的保守表明，这一途径在RNA沉默中发挥着古老和基础的作用。
The authors define a multiprotein nuclear RNA silencing (NURS) complex that mediates silencing of meiotic genes during vegetative growth in the fission yeast S. pombe. Meiotic gene silencing occurs post-transcriptionally through recruitment of the exosome complex to promote RNA degradation. Extensive interaction analysis and functional characterizations link the NURS complex to specific RNA-binding and processing proteins and also chromatin modification machinery. RNA is a central component of gene-silencing pathways that regulate diverse cellular processes. In the fission yeast Schizosaccharomyces pombe, an RNA-based mechanism represses meiotic gene expression during vegetative growth. This pathway depends on the zinc finger protein Red1, which is required to degrade meiotic mRNAs as well as to target histone H3 lysine 9 (H3K9) methylation, a repressive chromatin mark, to a subset of meiotic genes. However, the mechanism of Red1 function is unknown. Here we use affinity purification and mass spectrometry to identify a Red1-containing nuclear RNA silencing (NURS) complex. In addition to Red1, this complex includes the Mtl1, Red5, Ars2, Rmn1, and Iss10 proteins and associates with several other complexes that are involved in either signaling or mediating RNA silencing. By analyzing the effects of gene knockouts and inducible knockdown alleles, we show that NURS subunits regulate RNA degradation and H3K9 methylation at meiotic genes. We also identify roles for individual NURS subunits in interactions with Mmi1, an RNA-binding protein that marks meiotic RNAs for destruction, and the nuclear exosome RNA degradation complex. Finally, we show that the levels of H3K9 methylation at meiotic genes are not sufficient to restrict RNA polymerase II access or repress gene expression during vegetative growth. Our results demonstrate that Red1 partners with other proteins to silence meiotic gene expression at the post-transcriptional level. Conservation of a NURS-like complex in human cells suggests that this pathway plays an ancient and fundamental role in RNA silencing.
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影响因子：
64.5
作者：
Buehler, Marc;Haas, Wilhelm;Moazed, Danesh
通讯作者：
Moazed, Danesh
影响因子：
3.8
作者：
Cho, Ye-Seul;Jang, Sooyeon;Yoon, Jin Ho
通讯作者：
Yoon, Jin Ho
影响因子：
4.5
作者：
Keller, Claudia;Woolcock, Katrina;Buehler, Marc
通讯作者：
Buehler, Marc
DOI：
10.1073/pnas.0802493105
发表时间：
2008-06-24
影响因子：
11.1
作者：
Laubinger, Sascha;Sachsenberg, Tirno;Weigel, Detlef
通讯作者：
Weigel, Detlef
影响因子：
2.6
作者：
Hentges, P;Van Driessche, B;Carr, AM
通讯作者：
Carr, AM