Deletion of Human tarbp2 Reveals Cellular MicroRNA Targets and Cell-Cycle Function of TRBP

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TRBP functions as both a Dicer cofactor and a PKR inhibitor. However, the role of TRBP in microRNA (miRNA) biogenesis is controversial and its regulation of PKR in mitosis remains unexplored. Here, we generate TRBP knockout cells and find altered Dicer-processing sites in a subset of miRNAs but no effect on Dicer stability, miRNA abundance, or Argonaute loading. By generating PACT, another Dicer interactor, and TRBP/PACT double knockout (KO) cells, we further show that TRBP and PACT do not functionally compensate for one another and that only TRBP contributes to Dicer processing. We also report that TRBP is hyperphosphorylated by JNK in M phase when PKR is activated by cellular double-stranded RNAs (dsRNAs). Hyperphosphorylation potentiates the inhibitory activity of TRBP on PKR, suppressing PKR in M-G1 transition. By generating human TRBP KO cells, our study clarifies the role of TRBP and unveils negative feedback regulation of PKR through TRBP phosphorylation.
Publisher
Cell Press
Issue Date
2014-11
Language
English
Article Type
Article
Keywords

RNA-BINDING-PROTEIN; GUIDE STRAND SELECTION; DEPENDENT KINASE PKR; IN-VITRO; C-ELEGANS; MICROPROCESSOR COMPLEX; HUMAN DICER; INTERFERENCE; EXPRESSION; PHOSPHORYLATION

Citation

CELL REPORTS, v.9, pp.1061 - 1074

ISSN
2211-1247
DOI
10.1016/j.celrep.2014.09.039
URI
http://hdl.handle.net/10203/211808
Appears in Collection
CBE-Journal Papers(저널논문)
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