Enhancer of Rudimentary Cooperates with Conserved RNA-Processing Factors to Promote Meiotic mRNA Decay and Facultative Heterochromatin Assembly.
Enhancer of Rudimentary Cooperates with Conserved RNA-Processing Factors to Promote Meiotic mRNA Decay and Facultative Heterochromatin Assembly.
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DOI：
10.1016/j.molcel.2016.01.029
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发表时间：
2016-03-03
期刊：
影响因子：
16
通讯作者：
Grewal SIS
中科院分区：
文献类型：
--
作者：
Sugiyama T;Thillainadesan G;Chalamcharla VR;Meng Z;Balachandran V;Dhakshnamoorthy J;Zhou M;Grewal SIS
Erh 1是一种与发育增强子同源的裂殖酵母同源基因，参与营养生长过程中减数分裂mRNA的消除，但其功能尚不清楚。我们发现，Erh 1和RNA结合蛋白Mmi 1形成一个化学计量复合物称为EMC（Erh 1-Mmi 1复合物），以促进减数分裂mRNA衰变和兼性异染色质组装。为了执行这些功能，EMC与两个不同的复合体相关联，即MTREC（Mtl 1-Red 1核心）和CCR 4-NOT。MTREC促进异染色质岛的组装，异染色质岛覆盖被核外泌体沉默的减数分裂基因，而CCR 4-NOT促进EMC靶基因座处的RNAi依赖性异染色质结构域（HOOD）形成。CCR 4-NOT还在反转录转座子和含有隐蔽内含子的调节基因处组装HOOD。我们发现CCR 4-NOT通过与保守的Pir 2/ARS 2蛋白的结合促进HOOD组装，并且还通过促进异染色质形成来维持rDNA的完整性和沉默。我们的研究结果揭示了Erh 1，CCR 4-NOT，Pir 2/ARS 2和RNAi之间的联系，它们靶向异染色质以调节基因表达并保护基因组完整性。
Erh1, the fission yeast homolog of Enhancer of rudimentary, is implicated in meiotic mRNA elimination during vegetative growth, but its function is poorly understood. We show that Erh1 and the RNA-binding protein Mmi1 form a stoichiometric complex called EMC (Erh1-Mmi1 complex), to promote meiotic mRNA decay and facultative heterochromatin assembly. To perform these functions, EMC associates with two distinct complexes, MTREC (Mtl1-Red1 core) and CCR4-NOT. Whereas MTREC facilitates assembly of heterochromatin islands coating meiotic genes silenced by the nuclear exosome, CCR4-NOT promotes RNAi-dependent heterochromatin domain (HOOD) formation at EMC-target loci. CCR4-NOT also assembles HOODs at retrotransposons and regulated genes containing cryptic introns. We find that CCR4-NOT facilitates HOOD assembly through its association with the conserved Pir2/ARS2 protein, and also maintains rDNA integrity and silencing by promoting heterochromatin formation. Our results reveal connections among Erh1, CCR4-NOT, Pir2/ARS2 and RNAi, which target heterochromatin to regulate gene expression and to protect genome integrity.