Our discovery of a novel cytoplasmic domain in HEp-2 cells recognized by the autoimmune serum of a patient led us on a journey into the world of microRNAs (miRNA). Our journey began with the identification and cloning of the novel glycine (G)–tryptophan (W)-rich protein, GW182, and its close interaction with the miRNA-binding protein, argonaute2 (Ago2). Discovering the important relevance of GW...

The human GW182 protein plays an essential role in micro(mi)RNA-dependent gene silencing. miRNA silencing is mediated, in part, by a GW182 C-terminal region called the silencing domain, which interacts with the poly(A) binding protein and the CCR4-NOT deadenylase complex to repress protein synthesis. Structural studies of this GW182 fragment are challenging due to its predicted intrinsically di...

MicroRNAs (miRNAs) post-transcriptionally repress gene expression via the miRNA-induced silencing complex (miRISC), which includes miRNA, Argonaute and a GW182 family member. Here we show that in Caenorhabditis elegans, miRNA-mediated gene silencing is modulated by macroautophagy, a lysosome-mediated degradation process. Loss of autophagy activity suppresses developmental defects caused by part...

GW182 family proteins are essential for miRNA-mediated gene silencing in animal cells. They are recruited to miRNA targets via interactions with Argonaute proteins and then promote translational repression and degradation of the miRNA targets. The human and Drosophila melanogaster GW182 proteins share a similar domain organization and interact with PABPC1 as well as with subunits of the PAN2-PA...

As you will see, while the referees acknowledge that the finding that GW182 prevents miRNA degradation is potentially interesting, both referees 1 and 2 also point out that, as it stands, the manuscript is rather preliminary and requires significant strengthening before it can be considered for publication by EMBO reports. Both referees remark that endogenous miRNA levels need to be examined in...

In mammalian cells, the GW182 protein localizes to cytoplasmic bodies implicated in the regulation of messenger RNA (mRNA) stability, translation, and the RNA interference pathway. Many of these functions have also been assigned to analogous yeast cytoplasmic mRNA processing bodies. We have characterized the single Drosophila melanogaster homologue of the human GW182 protein family, which we ha...

The GW182/TNRC6 family of proteins are central scaffolds that link microRNA-associated Argonaute proteins to the cytoplasmic decay machinery for targeted mRNA degradation processes. Although nuclear roles for the GW182/TNRC6 proteins are unknown, recent reports have demonstrated nucleocytoplasmic shuttling activity that utilises the importin-α and importin-β transport receptors for nuclear tran...

GW182 family proteins play important roles in microRNA (miRNA)-mediated RNA silencing. They directly interact with Argonaute (Ago) proteins in processing bodies (P bodies), cytoplasmic foci involved in mRNA degradation and storage. Recently, we revealed that a human GW182 family protein, TNRC6A, is a nuclear-cytoplasmic shuttling protein, and its subcellular localization is regulated by its own...