Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies

Abstract

RNA interference (RNAi) is an important means of eliminating mRNAs, but the intracellular location of RNA-induced silencing complex (RISC) remains unknown. We show here that Argonaute 2, a key component of RISC, is not randomly distributed but concentrates in mRNA decay centres that are known as cytoplasmic bodies. The localization of Argonaute 2 in decay centres is not altered by the presence or absence of small interfering RNAs or their targeted mRNAs. However, RNA is required for the integrity of cytoplasmic bodies because RNase eliminates Argonaute 2 localization. In addition, Argonaute 1, another Argonaute family member, is concentrated in cytoplasmic bodies. These results provide new insight into the mechanism of RNAi function.

Principles and effects of microRNA-mediated post-transcriptional gene regulation

“…Human Argonaute proteins and C. elegans ALG-1, a worm Argonaute protein required for let-7-directed gene regulation, colocalize, co-purify and interact with proteins also located in PBs (Ding et al, 2005;Jakymiw et al, 2005;Sen and Blau, 2005;Liu et al, 2005a, b;Meister et al, 2005). The localization of Argonaute proteins to PBs requires that the protein bind small RNAs; the target mRNA is transported to the PB only if it contains miRNA-binding sites, suggesting that miRNAs bound to Argonaute proteins direct the mRNA to the PBs (Agbottah et al, 2005;Pillai et al, 2005;Liu et al, 2005a, b).…”

A genome-wide RNAi screen identifies genes regulating the formation of P bodies in C. elegans and their functions in NMD and RNAi

“…Cytoplasmic processing bodies, termed P bodies, are involved in mRNA degradation, nonsense-mediated RNA decay (NMD), siRNA-and micro-RNA (miRNA)-mediated gene silencing in mammalian cells (Sheth and Parker, 2003;Cougot et al, 2004;Jakymiw et al, 2005;Liu et al, 2005aLiu et al, , 2005bSen and Blau, 2005;Bruno and Wilkinson, 2006;Parker and Sheth, 2007). Consistently, P bodies contain components involved in 5' to 3' mRNA degradation, including the decapping complex DCAP1/ DCAP2, decapping coactivators (e.g.…”

MicroRNAs and genomic instability

“…The role of miRNAs in the regulation of gene expression is primarily thought to be through repression of translation, however, there is conflicting evidence as to whether miRNA activity is mediated through effects on the initiation of translation and/or termination [33][34][35]. In addition, miRNA mediated changes in gene expression may also involve RNA cleavage, RNA sequestration and/ or degradation of the transcript to P-bodies [36][37][38][39][40] (Fig. 1).…”