Defining a new role of GW182 in maintaining miRNA stability.

نویسندگان

  • Bing Yao
  • Lan B La
  • Ying-Chi Chen
  • Lung-Ji Chang
  • Edward K L Chan
چکیده

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.

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عنوان ژورنال:
  • EMBO reports

دوره 13 12  شماره 

صفحات  -

تاریخ انتشار 2012