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一种与前体 mRNA 相关的因子将内源性 siRNA 与染色质调控联系起来。

A pre-mRNA-associating factor links endogenous siRNAs to chromatin regulation.

机构信息

Laboratory of Genetics, University of Wisconsin Madison, Madison, Wisconsin, United States of America.

出版信息

PLoS Genet. 2011 Aug;7(8):e1002249. doi: 10.1371/journal.pgen.1002249. Epub 2011 Aug 25.

DOI:10.1371/journal.pgen.1002249
PMID:21901112
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3161925/
Abstract

In plants and fungi, small RNAs silence gene expression in the nucleus by establishing repressive chromatin states. The role of endogenous small RNAs in metazoan nuclei is largely unknown. Here we show that endogenous small interfering RNAs (endo-siRNAs) direct Histone H3 Lysine 9 methylation (H3K9me) in Caenorhabditis elegans. In addition, we report the identification and characterization of nuclear RNAi defective (nrde)-1 and nrde-4. Endo-siRNA-driven H3K9me requires the nuclear RNAi pathway including the Argonaute (Ago) NRDE-3, the conserved nuclear RNAi factor NRDE-2, as well as NRDE-1 and NRDE-4. Small RNAs direct NRDE-1 to associate with the pre-mRNA and chromatin of genes, which have been targeted by RNAi. NRDE-3 and NRDE-2 are required for the association of NRDE-1 with pre-mRNA and chromatin. NRDE-4 is required for NRDE-1/chromatin association, but not NRDE-1/pre-mRNA association. These data establish that NRDE-1 is a novel pre-mRNA and chromatin-associating factor that links small RNAs to H3K9 methylation. In addition, these results demonstrate that endo-siRNAs direct chromatin modifications via the Nrde pathway in C. elegans.

摘要

在植物和真菌中，小 RNA 通过建立抑制性染色质状态来沉默核内基因表达。内源性小 RNA 在后生动物核内的作用在很大程度上是未知的。在这里，我们表明内源性小干扰 RNA（endo-siRNA）指导秀丽隐杆线虫中的组蛋白 H3 赖氨酸 9 甲基化（H3K9me）。此外，我们报告了核 RNAi 缺陷（nrde）-1 和 nrde-4 的鉴定和特征。endo-siRNA 驱动的 H3K9me 需要包括 Argonaute（Ago）NRDE-3、保守的核 RNAi 因子 NRDE-2 以及 NRDE-1 和 NRDE-4 在内的核 RNAi 途径。小 RNA 指导 NRDE-1 与已被 RNAi 靶向的 pre-mRNA 和染色质结合。NRDE-3 和 NRDE-2 是 NRDE-1 与 pre-mRNA 和染色质结合所必需的。NRDE-4 是 NRDE-1/染色质结合所必需的，但不是 NRDE-1/pre-mRNA 结合所必需的。这些数据表明，NRDE-1 是一种将小 RNA 与 H3K9 甲基化联系起来的新型 pre-mRNA 和染色质结合因子。此外，这些结果表明，内源性 siRNA 通过 Nrde 途径在秀丽隐杆线虫中指导染色质修饰。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/3161925/cad31d04781b/pgen.1002249.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/3161925/e3b9ebf5594c/pgen.1002249.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/3161925/2642c63c6683/pgen.1002249.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/3161925/176f9bf42447/pgen.1002249.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/3161925/bb7076c6f9a8/pgen.1002249.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/3161925/505aab0bd856/pgen.1002249.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/3161925/cad31d04781b/pgen.1002249.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/3161925/e3b9ebf5594c/pgen.1002249.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/3161925/2642c63c6683/pgen.1002249.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/3161925/176f9bf42447/pgen.1002249.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/3161925/bb7076c6f9a8/pgen.1002249.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/3161925/505aab0bd856/pgen.1002249.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/3161925/cad31d04781b/pgen.1002249.g006.jpg

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