Description
Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis (PubMed:22701344, PubMed:22367205, PubMed:25505318, PubMed:24830504, PubMed:27102483). Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (By similarity). Functions by recruiting the CCR4-NOT deadenylase complex and probably other components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes (By similarity). Binds to 3'-UTR ARE of numerous mRNAs (PubMed:22701344, PubMed:22367205, PubMed:25505318, PubMed:24830504). Promotes ARE-containing mRNA decay of the low-density lipoprotein (LDL) receptor (LDLR) mRNA in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner (By similarity). Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs) (PubMed:22701344). Plays a role in mature peripheral neuron integrity by promoting ARE-containing mRNA decay of the transcriptional repressor REST mRNA (PubMed:25505318). Plays a role in ovulation and oocyte meiotic maturation by promoting ARE-mediated mRNA decay of the luteinizing hormone receptor LHCGR mRNA (PubMed:24830504). Acts as a negative regulator of erythroid cell differentiation: promotes glucocorticoid-induced self-renewal of erythroid cells by binding mRNAs that are induced or highly expressed during terminal erythroid differentiation and promotes their degradation, preventing erythroid cell differentiation (PubMed:19633199, PubMed:23748442). In association with ZFP36L1 maintains quiescence on developing B lymphocytes by promoting ARE-mediated decay of several mRNAs encoding cell cycle regulators that help B cells progress through the cell cycle, and hence ensuring accurate variable-diversity-joining (VDJ) recombination process and functional immune cell formation (PubMed:27102483). Together with ZFP36L1 is also necessary for thymocyte development and prevention of T-cell acute lymphoblastic leukemia (T-ALL) transformation by promoting ARE-mediated mRNA decay of the oncogenic transcription factor NOTCH1 mRNA (PubMed:20622884).
Sequence
MSTTLLSPFYDIDFLCKTEKSLANLNLNNMLDKKAVGTPVAAAPSSSFTPGFLRRHSASNLHALAHPVPSPGSCSPKFPGAPNGGGSSCGPAGGGGLASYGQLKEPSGGSGTALVTKESKFRDRSFSENGERSQHLLHLQQQQKGGSGSQINSTRYKTELCRPFEESGTCKYGEKCQFAHGFHELRSLTRHPKYKTELCRTFHTIGFCPYGPRCHFIHNADERRPAPSGGGGASGDLRAFGARDALHLGFAREPRPKLHHSLSFSGFPSGHHQPPGGLESPLLLDSPTSRTPPPPSSSASSCSSSASSCSSASAASTPSGAPTCCATAAAAALLYGPGGAEDLLSPGAPCASCSSSGANNAFAFGPELSSLITPLAIQTHNFAAAAAAAYYRNQQQGLTGPAPPPAQPPAAPAPPSPPFGFQLPRRLSESPVFDAPPSPPDSLSDRDSYLSGSLSSGSLSGSESPSLDPGRRLPIFSRLSISDD