RNA m6A修饰在调控Phytophthora sojae的发育、感染和氧化DNA损伤修复中的新作用。

IF 5.5 1区 医学 Q1 MICROBIOLOGY
PLoS Pathogens Pub Date : 2024-09-23 eCollection Date: 2024-09-01 DOI:10.1371/journal.ppat.1012553
Fan Zhang, Borui Zhang, Tongshan Cui, Shanshan Chen, Can Zhang, Zhiwen Wang, Xili Liu
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引用次数: 0

摘要

N6-甲基腺苷(m6A)是一种重要的转录后调节因子,是真核生物中最常见的 RNA 修饰之一。然而,人们对 m6A 在卵菌中的生物学功能仍然知之甚少。在这里,我们发现 PsMTA1 和 PsMTA2 基因是人类 METTL4 的直向同源物,而 PsMET16 基因是人类 METTL16 的直向同源物。这些基因参与了 m6A 的修饰,并在孢子囊和卵孢子的产生、子孢子的释放以及疫霉菌的毒力方面发挥了关键作用。在 P. sojae 中,m6A 修饰主要富集在编码序列和 3' 非翻译区。值得注意的是,PsMTA1基因敲除突变体的毒力减弱,这归因于其对宿主防御产生的ROS压力的耐受性减弱。从机理上讲,PsMTA1 介导的 m6A 修饰正向调节了 DNA 损伤应答(DDR)基因的 mRNA 寿命,以应对感染过程中的植物 ROS 胁迫。因此,在单个 m6A 位点突变体 ΔRCC1/RCC1A2961C 中,DDR 基因 PsRCC1 的 mRNA 丰度降低,导致 P. sojae 的 DNA 损伤修复能力受损,ROS 适应性相关毒力降低。总之,这些结果表明,m6A 介导的 RNA 代谢与 P. sojae 的发育和致病性有关,强调了表观遗传标记在感染期间噬菌体的适应灵活性中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The novel roles of RNA m6A modification in regulating the development, infection, and oxidative DNA damage repair of Phytophthora sojae.

N6-methyladenosine (m6A), a vital post-transcriptional regulator, is among the most prevalent RNA modifications in eukaryotes. Nevertheless, the biological functions of m6A in oomycetes remain poorly understood. Here, we showed that the PsMTA1 and PsMTA2 genes are orthologs of human METTL4, while the PsMET16 gene is an ortholog of human METTL16. These genes are implicated in m6A modification and play a critical role in the production of sporangia and oospores, the release of zoospores, and the virulence of Phytophthora sojae. In P. sojae, m6A modifications are predominantly enriched in the coding sequence and the 3' untranslated region. Notably, the PsMTA1 knockout mutant exhibited reduced virulence, attributed to impaired tolerance to host defense-generated ROS stress. Mechanistically, PsMTA1-mediated m6A modification positively regulates the mRNA lifespan of DNA damage response (DDR) genes in reaction to plant ROS stress during infection. Consequently, the mRNA abundance of the DDR gene PsRCC1 was reduced in the single m6A site mutant ΔRCC1/RCC1A2961C, resulting in compromised DNA damage repair and reduced ROS adaptation-associated virulence in P. sojae. Overall, these results indicate that m6A-mediated RNA metabolism is associated with the development and pathogenicity of P. sojae, underscoring the roles of epigenetic markers in the adaptive flexibility of Phytophthora during infection.

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来源期刊
PLoS Pathogens
PLoS Pathogens MICROBIOLOGY-PARASITOLOGY
自引率
3.00%
发文量
598
期刊介绍: Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.
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