State Key Laboratory of Maize Bio-breeding and Department of Plant Pathology, China Agricultural University, Beijing 100193, China.
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Sci Adv. 2024 Aug 23;10(34):eadn3010. doi: 10.1126/sciadv.adn3010.
The eukaryotic mRNA surveillance pathway, a pivotal guardian of mRNA fidelity, stands at the nexus of diverse biological processes, including antiviral immunity. Despite the recognized function of splicing factors on mRNA fate, the intricate interplay shaping the mRNA surveillance pathway remains elusive. We illustrate that the conserved splicing factor U2 snRNP auxiliary factor large subunit B (U2AF65B) modulates splicing of mRNA surveillance complex, contributing to transcriptomic homeostasis in maize. The functionality of the mRNA surveillance pathway requires ZmU2AF65B-mediated normal splicing of () pre-mRNA, encoding a core factor in this pathway. Intriguingly, sugarcane mosaic virus (SCMV)-coded nuclear inclusion protein a protease (NIa-Pro) hinders the splicing function of ZmU2AF65B. Furthermore, NIa-Pro disrupts ZmU2AF65B binding to pre-mRNA, leading to dysregulated splicing of transcripts and, consequently, impairing mRNA surveillance, thus facilitating viral infection. Together, this study establishes that splicing governs the mRNA surveillance pathway and identifies a pathogenic protein capable of disrupting this regulation to compromise RNA immunity.
真核生物 mRNA 监控途径是 mRNA 保真度的关键守护者,处于包括抗病毒免疫在内的多种生物过程的交汇点。尽管剪接因子对 mRNA 命运具有公认的功能,但塑造 mRNA 监控途径的复杂相互作用仍难以捉摸。我们表明,保守的剪接因子 U2 snRNP 辅助因子大亚基 B (U2AF65B) 调节 mRNA 监控复合物的剪接,有助于玉米中转录组的动态平衡。mRNA 监控途径的功能需要 ZmU2AF65B 介导的 () 前体 mRNA 的正常剪接,该前体 mRNA 编码该途径中的核心因子。有趣的是,甘蔗花叶病毒 (SCMV) 编码的核内含蛋白 a 蛋白酶 (NIa-Pro) 阻碍了 ZmU2AF65B 的剪接功能。此外,NIa-Pro 破坏了 ZmU2AF65B 与 前体 mRNA 的结合,导致 转录物的剪接失调,从而损害 mRNA 监控,从而促进病毒感染。总之,这项研究确立了剪接控制着 mRNA 监控途径,并确定了一种致病蛋白能够破坏这种调节,从而损害 RNA 免疫。