A member of the polymerase β nucleotidyltransferase superfamily is required for RNA interference in C-elegans
A member of the polymerase β nucleotidyltransferase superfamily is required for RNA interference in C-elegans
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DOI：
10.1016/j.cub.2005.01.009
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发表时间：
2005-02-22
期刊：
影响因子：
9.2
通讯作者：
Mello, CC
中科院分区：
文献类型：
--
作者：
Chen, CCG;Simard, MJ;Mello, CC
RNA干扰（RNAi）是一种古老的高度保守的机制，其中小RNA分子（siRNA）引导基因表达的序列特异性沉默[1]。已经鉴定了几种沉默机制蛋白组分，包括解旋酶、RNA酶相关蛋白、双链和单链RNA结合蛋白以及RNA依赖性RNA聚合酶相关蛋白[2]。对这些因素的研究揭示了RNAi机制与发育和生育所需的细胞途径交叉（3，4）。尽管在理解RNAi途径中的关键步骤方面取得了快速进展，但很明显，RNAi和相关发育机制所需的许多因素尚未确定。在这里，我们报告的C。线虫rde-3基因。假定无效等位基因的遗传分析表明，rde-3是siRNA积累和有效的RNAi在所有组织中所必需的，它是在高温下的生育力和生存力所必需的。RDE-3含有在聚合酶β核苷酸转移酶超家族中发现的保守结构域，该超家族包括常规聚腺苷酸聚合酶、2 '-5'寡腺苷酸合成酶（OAS）和酵母Trf 4p [5]。这些发现暗示了RNAi中的一种新的酶模式，并为RDE-3在RNAi机制中的作用提出了可能的模型。
RNA interference (RNAi) is an ancient, highly conserved mechanism in which small RNA molecules (siRNAs) guide the sequence-specific silencing of gene expression [1]. Several silencing machinery protein components have been identified, including helicases, RNase-related proteins, double- and singlestranded RNA binding proteins, and RNA-dependent RNA polymerase-related proteins [2]. Work on these factors has led to the revelation that RNAi mechanisms intersect with cellular pathways required for development and fertility (3, 4]. Despite rapid progress in understanding key steps in the RNAi pathway, it is clear that many factors required for both RNAi and related developmental mechanisms have not yet been identified. Here, we report the characterization of the C. elegans gene rde-3. Genetic analysis of presumptive null alleles indicates that rde-3 is required for siRNA accumulation and for efficient RNAi in all tissues, and it is essential for fertility and viability at high temperatures. RDE-3 contains conserved domains found in the polymerase beta nucleotidyltransferase superfamily, which includes conventional poly(A) polymerases, 2'-5' oligoadenylate synthetase (OAS), and yeast Trf4p [5]. These findings implicate a new enzymatic modality in RNAi and suggest possible models for the role of RDE-3 in the RNAi mechanism.