A member of the polymerase β nucleotidyltransferase superfamily is required for RNA interference in C-elegans

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.