title: hnRNP F complexes with tristetraprolin and stimulates ARE-mRNA decay.
abstract: The tristetraprolin (TTP) family of zinc-finger proteins, TTP, BRF1 and BRF2, regulate the stability of a subset of mRNAs containing 3'UTR AU-rich elements (AREs), including mRNAs coding for cytokines, transcription factors, and proto-oncogenes. To better understand the mechanism by which TTP-family proteins control mRNA stability in mammalian cells, we aimed to identify TTP- and BRF1-interacting proteins as potential TTP-family co-factors. This revealed hnRNP F as a prominent interactor of TTP and BRF1. While TTP, BRF1 and hnRNP F are all RNA binding proteins (RBPs), the interaction of hnRNP F with TTP and BRF1 is independent of RNA. Depletion of hnRNP F impairs the decay of a subset of TTP-substrate ARE-mRNAs by a mechanism independent of the extent of hnRNP F binding to the mRNA. Taken together, these findings implicate hnRNP F as a co-factor in a subset of TTP/BRF-mediated mRNA decay and highlight the importance of RBP cooperativity in mRNA regulation.
authors: Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
authors: Boris
authors: B
authors: Reznik
authors: Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
authors: Sandra L
authors: SL
authors: Clement
authors: Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
authors: Jens
authors: J
authors: Lykke-Andersen
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D006367:HeLa Cells; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000378:metabolism*; D035361:Transcription Factor TFIIIB / Q000235:genetics / Q000378:metabolism*; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C441028:BRF1 protein, human; C416185:BRF2 protein, human; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; D034741:RNA, Small Interfering; D035381:TATA-Binding Protein Associated Factors; D035361:Transcription Factor TFIIIB; D051816:Tristetraprolin; C497552:ZFP36 protein, human; D008156:Luciferases