Gut commensal bacteria-derived methionine is required for host reproduction by modulating RNA m6A methylation of the insulin receptor.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-06-24 DOI:10.1016/j.celrep.2025.115911

Qiuyuan Zhang, ZhuRong Deng, Xiaoxue Li, Jiao Qiao, Ziniu Li, Peipei Liu, Alfred M Handler, Bruno Lemaitre, Weiwei Zheng, Hongyu Zhang

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Abstract

Gut commensal bacteria promote host reproduction by modulating metabolism and nutrition, but the molecular mechanisms by which microbes regulate reproduction remain unclear. Here, we show that gut commensal bacteria promote host reproduction by providing the amino acid methionine, which controls the RNA m6A modification level of insulin receptor (InR) in the ovary of the invasive insect Bactrocera dorsalis. Antibiotic-treated B. dorsalis shows reduced RNA m6A methylation levels and methionine content, resulting in arrested ovarian development and decreased fecundity. The gut commensal bacterium Enterobacter hormaechei-derived metabolite methionine restores the decreased RNA m6A level and the reproductive defects. Notably, the knockdown of METTL3 and METTL14, two genes encoding the RNA m6A methyltransferases, reduces InR mRNA and protein levels and impairs ovarian development in B. dorsalis. Our findings further expand the functional landscape of RNA m6A modification to include nutrient-dependent control of ovarian development and highlight the essential role of epigenetic regulation in microbe-host interactions.

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肠道共生细菌衍生的蛋氨酸是通过调节胰岛素受体的RNA m6A甲基化来实现宿主繁殖所必需的。

肠道共生菌通过调节代谢和营养促进宿主繁殖，但微生物调节繁殖的分子机制尚不清楚。在这里，我们发现肠道共生菌通过提供氨基酸蛋氨酸来促进宿主繁殖，蛋氨酸可以控制入侵昆虫小实蝇卵巢中胰岛素受体（InR）的RNA m6A修饰水平。抗生素处理的桃芽孢杆菌显示RNA m6A甲基化水平和蛋氨酸含量降低，导致卵巢发育受阻和繁殖力下降。肠道共生细菌hormaechei-肠杆菌衍生的代谢物蛋氨酸可恢复RNA m6A水平下降和生殖缺陷。值得注意的是，METTL3和METTL14这两个编码RNA m6A甲基转移酶的基因的敲低，降低了InR mRNA和蛋白水平，并损害了dorsalis的卵巢发育。我们的研究结果进一步扩展了RNA m6A修饰的功能景观，包括卵巢发育的营养依赖控制，并强调了表观遗传调控在微生物-宿主相互作用中的重要作用。

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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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.