title: Autoantigen La promotes efficient RNAi, antiviral response, and transposon silencing by facilitating multiple-turnover RISC catalysis.
abstract: The effector of RNA interference (RNAi) is the RNA-induced silencing complex (RISC). C3PO promotes the activation of RISC by degrading the Argonaute2 (Ago2)-nicked passenger strand of duplex siRNA. Active RISC is a multiple-turnover enzyme that uses the guide strand of siRNA to direct the Ago2-mediated sequence-specific cleavage of complementary mRNA. How this effector step of RNAi is regulated is currently unknown. Here, we used the human Ago2 minimal RISC system to purify Sjögren's syndrome antigen B (SSB)/autoantigen La as an activator of the RISC-mediated mRNA cleavage activity. Our reconstitution studies showed that La could promote multiple-turnover RISC catalysis by facilitating the release of cleaved mRNA from RISC. Moreover, we demonstrated that La was required for efficient RNAi, antiviral defense, and transposon silencing in vivo. Taken together, the findings of C3PO and La reveal a general concept that regulatory factors are required to remove Ago2-cleaved products to assemble or restore active RISC.
authors: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Ying
authors: Y
authors: Liu
authors: Huiling
authors: H
authors: Tan
authors: Hui
authors: H
authors: Tian
authors: Chunyang
authors: C
authors: Liang
authors: She
authors: S
authors: Chen
authors: Qinghua
authors: Q
authors: Liu
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism*; D002384:Catalysis; D004251:DNA Transposable Elements; D004330:Drosophila / Q000235:genetics / Q000378:metabolism / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D000097585:SS-B Antigen
chemical_list: D060565:Argonaute Proteins; D001324:Autoantigens; D004251:DNA Transposable Elements; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012367:RNA, Viral; D034743:RNA-Induced Silencing Complex; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; C466422:AGO2 protein, human