Circular RNA circTmem241 drives group III innate lymphoid cell differentiation via initiation of Elk3 transcription.
Circular RNA circTmem241 drives group III innate lymphoid cell differentiation via initiation of Elk3 transcription.
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环状RNA circTmem241通过启动Elk3转录驱动III组先天淋巴细胞分化
DOI：
10.1038/s41467-022-32322-z
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发表时间：
2022-08-11
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
先天淋巴样细胞（ILCs）在宿主防御、组织修复和炎症性疾病中发挥重要作用。然而，ILC谱系规范是如何调节的，在很大程度上仍然是难以捉摸的。本研究发现环状RNA circTmem241在III组先天淋巴样细胞（ILC3s）及其祖细胞中高度表达。CircTmem241缺乏会损害ILC3的作用并减弱抗菌免疫。在ILC前体细胞（ILCPs）中，circTmem241与Nono蛋白相互作用，将组蛋白甲基转移酶Ash1l募集到Elk3启动子上。在Elk3启动子上，ash1l介导的组蛋白修饰增强了染色质可及性，从而启动Elk3转录。值得注意的是，circTmem241−/−，Nono−/−和Ash1l−/−ILCPs显示ILC3分化受损，而Elk3过表达挽救了ILC3的承诺能力。最后，circTmem241−/−Elk3−/−小鼠显示出较低的ILC3s数量，并且更容易受到细菌感染。我们发现circTmem241-Nono-Ash1l-Elk3轴是ILCP分化为ILC3P和ILC3成熟所必需的，这对于控制该轴对ILC治疗感染性疾病的发展至关重要。先天淋巴样细胞（ILC）已被证明参与一系列炎症环境，但其细胞谱系如何被调节尚不完全确定。在这里，作者展示了环状RNA circTmem241通过启动Elk3转录在ILC3分化中的作用。
Innate lymphoid cells (ILCs) exert important roles in host defense, tissue repair and inflammatory diseases. However, how ILC lineage specification is regulated remains largely elusive. Here we identify that circular RNA circTmem241 is highly expressed in group III innate lymphoid cells (ILC3s) and their progenitor cells. CircTmem241 deficiency impairs ILC3 commitment and attenuates anti-bacterial immunity. Mechanistically, circTmem241 interacts with Nono protein to recruit histone methyltransferase Ash1l onto Elk3 promoter in ILC progenitor cells (ILCPs). Ash1l-mediated histone modifications on Elk3 promoter enhance chromatin accessibility to initiate Elk3 transcription. Of note, circTmem241−/−, Nono−/− and Ash1l−/− ILCPs display impaired ILC3 differentiation, while Elk3 overexpression rescues ILC3 commitment ability. Finally, circTmem241−/−Elk3−/− mice show lower numbers of ILC3s and are more susceptible to bacterial infection. We reveal that the circTmem241-Nono-Ash1l-Elk3 axis is required for the ILCP differentiation into ILC3P and ILC3 maturation, which is important to manipulate this axis for ILC development on treatment of infectious diseases. Innate lymphoid cells (ILC) have been shown to be involved in a range of inflammatory contexts but how their cellular lineage is regulated is not fully established. Here the authors show a role for circular RNA circTmem241 in the differentiation of ILC3 via initiation of Elk3 transcription.
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DOI：
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发表时间：
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期刊：
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