Disruption of GW bodies impairs mammalian RNA interference.
The GW182 RNA-binding protein was initially shown to associate with a specific subset of mRNAs and to reside within discrete cytoplasmic foci named GW bodies (GWBs). GWBs are enriched in proteins that are involved in mRNA degradation. Recent reports have shown that exogenously introduced human Argonaute-2 (Ago2) is also enriched in GWBs, indicating that RNA interference function may be somehow linked to these structures. In this report, we demonstrate that endogenous Ago2 and transfected small interfering RNAs (siRNAs) are also present within these same cytoplasmic bodies and that the GW182 protein interacts with Ago2. Disruption of these cytoplasmic foci in HeLa cells interferes with the silencing capability of a siRNA that is specific to lamin-A/C. Our data support a model in which GW182 and/or the microenvironment of the cytoplasmic GWBs contribute to the RNA-induced silencing complex and to RNA silencing.
Jakymiw
Andrew
A
Department of Oral Biology, University of Florida, Gainesville, FL 32610, USA.
Lian
Shangli
S
Eystathioy
Theophany
T
Li
Songqing
S
Satoh
Minoru
M
Hamel
John C
JC
Fritzler
Marvin J
MJ
Chan
Edward K L
EK
D060565:Argonaute Proteins; D001324:Autoantigens / Q000378:metabolism / Q000502:physiology*; D022083:Cytoplasmic Structures / Q000737:chemistry / Q000502:physiology*; D015852:Eukaryotic Initiation Factor-2; D006367:HeLa Cells; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D010448:Peptide Initiation Factors / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins
C466422:AGO2 protein, human; D060565:Argonaute Proteins; D001324:Autoantigens; D015852:Eukaryotic Initiation Factor-2; D034904:Lamin Type A; D010448:Peptide Initiation Factors; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C465663:TNRC6A protein, human; C440308:lamin C