【紹介文献】
Cues from mRNA splicing prevent default Argonaute silencing in C. elegans
Makeyev et al., 2021 Dev Cell, v56, p2636-2648
【発表概要】
RNAiはCraig C. Mello博士とAndrew Fire博士によってC. elegansではじめて発見されました。Craig C. Mello博士はその後も、RNAiの分子機構や生物学的意義について多くの報告をしています。今回はその中から、アルゴノートによる遺伝子サイレンシングがスプライシングによって阻害されることを報告した論文を紹介します。論文中では、スプライシングによるサイレンシングの阻害とgermline surveillance(生殖系列において外来遺伝子をサイレンシングしendogenousな遺伝子の発現は維持する仕組み)との関係についても議論されています。
【Summary】
In animals, Argonaute small-RNA pathways scan germline transcripts to silence self-replicating genetic elements. However, little is known about how endogenous gene expression is recognized and licensed. Here, they show that the presence of introns and, by inference, the process of mRNA splicing prevents default Argonaute-mediated silencing in the C. elegans germline. The silencing of intronless genes is initiated independently of the piRNA pathway but nevertheless engages multiple components of the downstream amplification and maintenance mechanisms that mediate transgenerational silencing, including both nuclear and cytoplasmic members of the worm-specific Argonaute gene family (WAGOs). Small RNAs amplified from intronless mRNAs can trans-silence cognate intron-containing genes. Interestingly, a second, small RNA-independent cis-acting mode of silencing also acts on intronless mRNAs. Our findings suggest that cues put in place during mRNA splicing license germline gene expression and provide evidence for a splicing-dependent and dsRNA- and piRNA-independent mechanism that can program Argonaute silencing.
(2022.7.7 Shonan iPark Science Cafe 120th)
