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Citation
Lee, Y.S., Pressman, S., Andress, A.P., Kim, K., White, J.L., Cassidy, J.J., Li, X., Lubell, K., Lim, D.H., Cho, I.S., Nakahara, K., Preall, J.B., Bellare, P., Sontheimer, E.J., Carthew, R.W. (2009). Silencing by small RNAs is linked to endosomal trafficking.  Nat. Cell Biol. 11(9): 1150--1156.
FlyBase ID
FBrf0208810
Publication Type
Research paper
Abstract

Small RNAs direct RNA-induced silencing complexes (RISCs) to regulate stability and translation of mRNAs. RISCs associated with target mRNAs often accumulate in discrete cytoplasmic foci known as GW-bodies. However, RISC proteins can associate with membrane compartments such as the Golgi and endoplasmic reticulum. Here, we show that GW-bodies are associated with late endosomes (multivesicular bodies, MVBs). Blocking the maturation of MVBs into lysosomes by loss of the tethering factor HPS4 (ref. 5) enhances short interfering RNA (siRNA)- and micro RNA (miRNA)-mediated silencing in Drosophila melanogaster and humans. It also triggers over-accumulation of GW-bodies. Blocking MVB formation by ESCRT (endosomal sorting complex required for transport) depletion results in impaired miRNA silencing and loss of GW-bodies. These results indicate that active RISCs are physically and functionally coupled to MVBs. We further show that MVBs promote the competence of RISCs in loading small RNAs. We suggest that the recycling of RISCs is promoted by MVBs, resulting in RISCs more effectively engaging with small RNA effectors and possibly target RNAs. It may provide a means to enhance the dynamics of RNA silencing in the cytoplasm.

PubMed ID
PubMed Central ID
PMC2737091 (PMC) (EuropePMC)
Related Publication(s)
Note

RISC hitches onto endosome trafficking.
Siomi and Siomi, 2009, Nat. Cell Biol. 11(9): 1049--1051 [FBrf0208787]

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Cell Biol.
    Title
    Nature Cell Biology
    Publication Year
    1999-
    ISBN/ISSN
    1465-7392 1476-4679
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    Alleles (17)
    Genes (22)
    Physical Interactions (2)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (2)
    Transgenic Constructs (4)