Defining a new role of GW182 in maintaining miRNA stability
Defining a new role of GW182 in maintaining miRNA stability
GW182 binds to Argonaute (AGO) proteins and has a central role in miRNA-mediated gene silencing. Using lentiviral shRNA-induced GW182 knockdown in HEK293 cells, this study identifies a new role of GW182 in regulating miRNA stability. Stably knocking down GW182 or its paralogue TNRC6B reduces transfected miRNA-mimic half-lives. Replenishment of GW182 family proteins, as well as one of its domain Δ12, significantly restores the stability of transfected miRNA-mimic. GW182 knockdown reduces miRNA secretion via secretory exosomes. Targeted siRNA screening identifies a 3'-5' exoribonuclease complex responsible for the miRNA degradation only when GW182 is knocked down. Immunoprecipitation further confirms that the presence of GW182 in the RISC complex is critical in protecting Argonaute-bound miRNA.
- University of Florida United States
Exonucleases, RNA Stability, RNA-Binding Proteins, Carboxypeptidases, Autoantigens, MicroRNAs, HEK293 Cells, Gene Knockdown Techniques, Argonaute Proteins, Humans, RNA, Small Interfering
Exonucleases, RNA Stability, RNA-Binding Proteins, Carboxypeptidases, Autoantigens, MicroRNAs, HEK293 Cells, Gene Knockdown Techniques, Argonaute Proteins, Humans, RNA, Small Interfering
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