The long noncoding RNA Malat1 regulates CD8+ T cell differentiation by mediating epigenetic repression.

The Tokushima journal of experimental medicine Pub Date : 2022-06-06 Epub Date: 2022-05-20 DOI:10.1084/jem.20211756
Jad N Kanbar, Shengyun Ma, Eleanor S Kim, Nadia S Kurd, Matthew S Tsai, Tiffani Tysl, Christella E Widjaja, Abigail E Limary, Brian Yee, Zhaoren He, Yajing Hao, Xiang-Dong Fu, Gene W Yeo, Wendy J Huang, John T Chang
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Abstract

During an immune response to microbial infection, CD8+ T cells give rise to short-lived effector cells and memory cells that provide sustained protection. Although the transcriptional programs regulating CD8+ T cell differentiation have been extensively characterized, the role of long noncoding RNAs (lncRNAs) in this process remains poorly understood. Using a functional genetic knockdown screen, we identified the lncRNA Malat1 as a regulator of terminal effector cells and the terminal effector memory (t-TEM) circulating memory subset. Evaluation of chromatin-enriched lncRNAs revealed that Malat1 grouped with trans lncRNAs that exhibit increased RNA interactions at gene promoters and gene bodies. Moreover, we observed that Malat1 was associated with increased H3K27me3 deposition at a number of memory cell-associated genes through a direct interaction with Ezh2, thereby promoting terminal effector and t-TEM cell differentiation. Our findings suggest an important functional role of Malat1 in regulating CD8+ T cell differentiation and broaden the knowledge base of lncRNAs in CD8+ T cell biology.

长非编码 RNA Malat1 通过介导表观遗传抑制调节 CD8+ T 细胞分化。
在对微生物感染的免疫反应过程中,CD8+ T 细胞会产生短效效应细胞和记忆细胞,从而提供持续的保护。尽管调控 CD8+ T 细胞分化的转录程序已被广泛表征,但人们对长非编码 RNA(lncRNA)在这一过程中的作用仍然知之甚少。通过功能性基因敲除筛选,我们发现lncRNA Malat1是末端效应细胞和末端效应记忆(t-TEM)循环记忆亚群的调控因子。对染色质富集的lncRNA进行评估后发现,Malat1与反式lncRNA组成一组,它们在基因启动子和基因体上表现出更多的RNA相互作用。此外,我们还观察到 Malat1 通过与 Ezh2 的直接相互作用,与一些记忆细胞相关基因的 H3K27me3 沉积增加有关,从而促进末端效应细胞和 t-TEM 细胞的分化。我们的研究结果表明,Malat1在调控CD8+ T细胞分化中具有重要的功能作用,并拓宽了lncRNA在CD8+ T细胞生物学中的知识基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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