细胞质 Argonaute 蛋白促进 RNAi 的遗传。

A Cytoplasmic Argonaute Protein Promotes the Inheritance of RNAi.

机构信息

Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.

Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China; CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Beijing, China.

出版信息

Cell Rep. 2018 May 22;23(8):2482-2494. doi: 10.1016/j.celrep.2018.04.072.

DOI:10.1016/j.celrep.2018.04.072

PMID:29791857

Abstract

RNAi-elicited gene silencing is heritable and can persist for multiple generations after its initial induction in C. elegans. However, the mechanism by which parental-acquired trait-specific information from RNAi is inherited by the progenies is not fully understood. Here, we identified a cytoplasmic Argonaute protein, WAGO-4, necessary for the inheritance of RNAi. WAGO-4 exhibits asymmetrical translocation to the germline during early embryogenesis, accumulates at the perinuclear foci in the germline, and is required for the inheritance of exogenous RNAi targeting both germline- and soma-expressed genes. WAGO-4 binds to 22G-RNAs and their mRNA targets. Interestingly, WAGO-4-associated endogenous 22G-RNAs target the same cohort of germline genes as CSR-1 and contain untemplated addition of uracil at the 3' ends. The poly(U) polymerase CDE-1 is required for the untemplated uridylation of 22G-RNAs and inheritance of RNAi. Therefore, we conclude that, in addition to the nuclear RNAi pathway, the cytoplasmic RNAi machinery also promotes RNAi inheritance.

摘要

RNAi 引发的基因沉默是可遗传的，并且在 C. elegans 中最初诱导后可以持续多代。然而，RNAi 从亲代获得的特定于性状的信息如何被后代遗传的机制尚未完全理解。在这里，我们鉴定了一种细胞质 Argonaute 蛋白 WAGO-4，它是 RNAi 遗传所必需的。WAGO-4 在早期胚胎发生期间表现出不对称地向生殖系的易位，在生殖系的核周焦点处积累，并需要遗传针对生殖系和体细胞表达基因的外源 RNAi。WAGO-4 与 22G-RNAs 及其 mRNA 靶标结合。有趣的是，WAGO-4 相关的内源性 22G-RNAs 靶向与 CSR-1 相同的生殖系基因群，并在 3'末端含有未模板化的尿嘧啶添加。多聚（U）聚合酶 CDE-1 是 22G-RNAs 未模板化尿嘧啶化和 RNAi 遗传所必需的。因此，我们得出结论，除了核 RNAi 途径外，细胞质 RNAi 机制也促进了 RNAi 遗传。