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一类蛋白质编码RNA与多梳抑制复合物2结合并改变组蛋白甲基化。

A Class of Protein-Coding RNAs Binds to Polycomb Repressive Complex 2 and Alters Histone Methylation.

作者信息

Liao Meijian, Sun Xiaolin, Gao Shoucui, Zhang Yaou

机构信息

Department of Pathology, Xuzhou Medical University, Xuzhou, China.

State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China.

出版信息

Front Oncol. 2021 Nov 5;11:739830. doi: 10.3389/fonc.2021.739830. eCollection 2021.

DOI:10.3389/fonc.2021.739830
PMID:34804929
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8602814/
Abstract

Polycomb repressive complex 2 (PRC2) is a multi-subunit protein complex mediating the methylation of lysine 27 on histone H3 and playing an important role in transcriptional repression during tumorigenesis and development. Previous studies revealed that both protein-coding and non-coding RNAs could bind to PRC2 complex. However, the functions of protein-coding RNAs that bind to PRC2 complex in tumor are still unknown. Through data mining and RNA immunoprecipitation (RIP) assay, our study found that there were a class of protein-coding RNAs bound to PRC2 complex and H3 with tri-methylation on lysine 27. The Bayesian gene regulatory network analysis pointed out that these RNAs regulated the expression of PRC2-regulated genes in cancer. In addition, gene set enrichment analysis (GSEA), gene ontology (GO) analysis, and weighted gene co-expression network analysis (WGCNA) also confirmed that these RNAs were associated with histone modification in cancer. We also confirmed that MYO1C, a PRC2-bound transcript, inhibited the modification level of H3K27me3. Further detailed study showed that TMEM117 regulated TSLP expression through EZH2-mediated H3K27me3 modification. Interestingly, the RNA recognition motif of PRC2 complex might help these RNAs bind to the PRC2 complex more easily. The same regulatory pattern was found in mice as well.

摘要

多梳抑制复合物2（PRC2）是一种多亚基蛋白质复合物，介导组蛋白H3赖氨酸27位的甲基化，并在肿瘤发生和发展过程中的转录抑制中发挥重要作用。先前的研究表明，蛋白质编码RNA和非编码RNA都可以与PRC2复合物结合。然而，在肿瘤中与PRC2复合物结合的蛋白质编码RNA的功能仍不清楚。通过数据挖掘和RNA免疫沉淀（RIP）分析，我们的研究发现有一类蛋白质编码RNA与PRC2复合物和赖氨酸27位三甲基化的H3结合。贝叶斯基因调控网络分析指出，这些RNA在癌症中调节PRC2调控基因的表达。此外，基因集富集分析（GSEA）、基因本体（GO）分析和加权基因共表达网络分析（WGCNA）也证实这些RNA与癌症中的组蛋白修饰有关。我们还证实，与PRC2结合的转录本MYO1C抑制了H3K27me³的修饰水平。进一步的详细研究表明，跨膜蛋白117（TMEM117）通过EZH2介导的H3K27me³修饰调节胸腺基质淋巴细胞生成素（TSLP）的表达。有趣的是，PRC2复合物的RNA识别基序可能有助于这些RNA更易与PRC2复合物结合。在小鼠中也发现了相同的调控模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29a/8602814/a1abfdab8ac4/fonc-11-739830-g008.jpg
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