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LSM2-8 and XRN-2 contribute to the silencing of H3K27me3-marked genes through targeted RNA decay.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2020-04-06 , DOI: 10.1038/s41556-020-0504-1
Anna Mattout 1, 2 , Dimos Gaidatzis 1, 3 , Jan Padeken 1 , Christoph D Schmid 1 , Florian Aeschimann 1, 4 , Véronique Kalck 1 , Susan M Gasser 1, 4
Affiliation  

In fission yeast and plants, RNA processing and degradation contribute to heterochromatin silencing, alongside conserved pathways of transcriptional repression. It has not been known whether similar pathways exist in metazoans. Here, we describe a pathway of silencing in Caenorhabditis elegans somatic cells, in which the highly conserved RNA-binding complex LSM2-8 contributes selectively to the repression of heterochromatic reporters and endogenous genes bearing the Polycomb mark, histone H3K27me3. This acts by degrading selected transcripts through the XRN-2 exoribonuclease. Disruption of the LSM2-8 pathway leads to mRNA stabilization. Unlike previously described pathways of heterochromatic RNA degradation, LSM2-8-mediated RNA degradation does not target nor require H3K9 methylation. Intriguingly, loss of this pathway coincides with a localized reduction in H3K27me3 at lsm-8-sensitive loci. We have thus uncovered a mechanism of RNA degradation that selectively contributes to the silencing of a subset of H3K27me3-marked genes, revealing a previously unrecognized layer of post-transcriptional control in metazoan heterochromatin.

中文翻译:

LSM2-8和XRN-2通过有针对性的RNA衰变有助于H3K27me3标记的基因沉默。

在裂变酵母和植物中,RNA加工和降解会导致异染色质沉默,以及保守的转录抑制途径。尚不清楚后生动物中是否存在类似的途径。在这里,我们描述了秀丽隐杆线虫体细胞中的沉默途径,其中高度保守的RNA结合复合物LSM2-8选择性地抑制异色报告基因和带有Polycomb标记的组蛋白H3K27me3的内源基因。这是通过XRN-2外切核糖核酸酶降解选定的转录本而起作用的。LSM2-8途径的破坏导致mRNA稳定。与先前描述的异色RNA降解途径不同,LSM2-8介导的RNA降解既不靶向也不要求H3K9甲基化。有趣的是 该途径的丧失与在lsm-8敏感基因座处的H3K27me3的局部减少相吻合。因此,我们发现了RNA降解的机制,该机制可选择性地使H3K27me3标记的基因的一个子集沉默,从而揭示了后生异染色质中转录后控制的先前未被认识的层。
更新日期:2020-04-24
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