title: Deletion of human tarbp2 reveals cellular microRNA targets and cell-cycle function of TRBP.
abstract: 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.
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, South Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Yoosik
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, South Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Jinah
authors.initials: J
authors.lastname: Yeo
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, South Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, South Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Cho
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, South Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Daekwan
authors.initials: D
authors.lastname: Seo
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, South Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Jong-Seo
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, South Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea. Electronic address: narrykim@snu.ac.kr.
authors.forename: V Narry
authors.initials: VN
authors.lastname: Kim
mesh_terms: D001483:Base Sequence; D002453:Cell Cycle; D049109:Cell Proliferation; D004720:Endonucleases / Q000378:metabolism; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism; D000099253:Trans-Activation Responsive RNA-Binding Protein
chemical_list: D004720:Endonucleases; D048031:JNK Mitogen-Activated Protein Kinases; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D043244:Ribonuclease III; D015534:Trans-Activators; D019892:eIF-2 Kinase; D000099253:Trans-Activation Responsive RNA-Binding Protein; C104647:PRKRA protein, human