Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity - PubMed (original) (raw)

Comment

doi: 10.1038/ncb1929. Epub 2009 Aug 16.

Affiliations

Comment

Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity

Derrick J Gibbings et al. Nat Cell Biol. 2009 Sep.

Erratum in

Abstract

In animals, P-bodies or GW-bodies appear to cause the congregation of proteins involved in microRNA (miRNA)-mediated post-transcriptional silencing. The localization of P-bodies does not overlap with that of known organelles and are thus considered independent of lipid bilayers. Nonetheless, an miRNA effector protein, argonaute 2 (AGO2), was initially identified as membrane-associated, and some miRNAs have been found in secreted vesicles (exosomes) that derive from endo-lysosomal compartments called multivesicular bodies (MVBs). Proteins can be sorted in a ubiquitin-dependent manner into MVBs by three heteromeric subcomplexes, collectively termed ESCRT (endosomal sorting complex required for transport), to be further secreted in exosomes and/or degraded by the lysosome. Here we show that GW-bodies containing GW182 and AGO2, two main components of the RNA-induced silencing complex (RISC), are distinct from P-bodies due to their congregation with endosomes and MVBs. Moreover, miRNAs and miRNA-repressible mRNAs are enriched at these cellular membranes, suggesting that endosomes and/or MVBs are sites of miRNA-loaded RISC (miRISC) accumulation and, possibly, action. We further show that purified exosome-like vesicles secreted by MVBs are considerably enriched in GW182, but not P-body components, AGO2 or miRNA-repressible mRNA. Moreover, cells depleted of some ESCRT components show compromised miRNA-mediated gene silencing and over-accumulate GW182, which associates with ubiquitylated proteins. Therefore, GW182, possibly in association with a fraction of miRNA-loaded AGO2, is sorted into MVBs for secretion and/or lysosomal degradation. We propose that this process promotes continuous assembly or disassembly of membrane-associated miRISCs, which is possibly required for miRNA loading or target recognition and subsequent silencing.

PubMed Disclaimer

Comment in

Comment on

Similar articles

Cited by

References

    1. Nat Cell Biol. 2008 Dec;10(12):1470-6 - PubMed
    1. Nat Rev Immunol. 2002 Aug;2(8):569-79 - PubMed
    1. Nat Struct Mol Biol. 2008 Apr;15(4):346-53 - PubMed
    1. Clin Exp Immunol. 2006 Mar;143(3):572-84 - PubMed
    1. PLoS Biol. 2006 Jul;4(7):e210 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources