title: The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function.
abstract: TRIM-NHL proteins are conserved regulators of development and differentiation but their molecular function has remained largely elusive. Here, we report an as yet unrecognized activity for the mammalian TRIM-NHL protein TRIM71 as a repressor of mRNAs. We show that TRIM71 is associated with mRNAs and that it promotes translational repression and mRNA decay. We have identified Rbl1 and Rbl2, two transcription factors whose down-regulation is important for stem cell function, as TRIM71 targets in mouse embryonic stem cells. Furthermore, one of the defining features of TRIM-NHL proteins, the NHL domain, is necessary and sufficient to target TRIM71 to RNA, while the RING domain that confers ubiquitin ligase activity is dispensable for repression. Our results reveal strong similarities between TRIM71 and Drosophila BRAT, the best-studied TRIM-NHL protein and a well-documented translational repressor, suggesting that BRAT and TRIM71 are part of a family of mRNA repressors regulating proliferation and differentiation.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland. inga.loedige@vkl.uni-regensburg.de
authors.forename: Inga
authors.initials: I
authors.lastname: Loedige
authors.forename: Dimos
authors.initials: D
authors.lastname: Gaidatzis
authors.forename: Ragna
authors.initials: R
authors.lastname: Sack
authors.forename: Gunter
authors.initials: G
authors.lastname: Meister
authors.forename: Witold
authors.initials: W
authors.lastname: Filipowicz
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D017354:Point Mutation; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors; D012261:Ribonucleoproteins / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C511366:LIN-41 protein, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D014157:Transcription Factors; C026452:messenger ribonucleoprotein