Mammalian GW220/TNGW1 is essential for the formation of GW/P bodies containing miRISC.
The microRNA (miRNA)-induced silencing complex (miRISC) controls gene expression by a posttranscriptional mechanism involving translational repression and/or promoting messenger RNA (mRNA) deadenylation and degradation. The GW182/TNRC6 (GW) family proteins are core components of the miRISC and are essential for miRNA function. We show that mammalian GW proteins have distinctive functions in the miRNA pathway, with GW220/TNGW1 being essential for the formation of GW/P bodies containing the miRISC. miRISC aggregation and formation of GW/P bodies sequestered and stabilized translationally repressed target mRNA. Depletion of GW220 led to the loss of GW/P bodies and destabilization of miRNA-targeted mRNA. These findings support a model in which the cellular localization of the miRISC regulates the fate of the target mRNA.
Cell Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Virginia
V
Castilla-Llorente
Lee
L
Spraggon
Miwako
M
Okamura
Saif
S
Naseeruddin
Matthew
M
Adamow
Sarah
S
Qamar
Jidong
J
Liu
D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology*; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000502:physiology*
D001324:Autoantigens; D035683:MicroRNAs; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; C465663:TNRC6A protein, human