title: LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms.
abstract: The RNA-binding protein (RBP) LIN41, also known as LIN-41 or TRIM71, is a key regulator of animal development, but its physiological targets and molecular mechanism of action are largely elusive. Here we find that this RBP has two distinct mRNA-silencing activities. Using genome-wide ribosome profiling, RNA immunoprecipitation, and in vitro-binding experiments, we identify four mRNAs, each encoding a transcription factor or cofactor, as direct physiological targets of C. elegans LIN41. LIN41 silences three of these targets through their 3' UTRs, but it achieves isoform-specific silencing of one target, lin-29A, through its unique 5' UTR. Whereas the 3' UTR targets mab-10, mab-3, and dmd-3 undergo transcript degradation, lin-29A experiences translational repression. Through binding site transplantation experiments, we demonstrate that it is the location of the LIN41-binding site that specifies the silencing mechanism. Such position-dependent dual activity may, when studied more systematically, emerge as a feature shared by other RBPs.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Faculty of Science, 4056 Basel, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Aeschimann
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Pooja
authors.initials: P
authors.lastname: Kumari
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Faculty of Science, 4056 Basel, Switzerland.
authors.forename: Hrishikesh
authors.initials: H
authors.lastname: Bartake
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; Swiss Institute of Bioinformatics, 4058 Basel, Switzerland.
authors.forename: Dimos
authors.initials: D
authors.lastname: Gaidatzis
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Lan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Ciosk
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. Electronic address: helge.grosshans@fmi.ch.
authors.forename: Helge
authors.initials: H
authors.lastname: Großhans
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D034622:RNA Interference; D020871:RNA Stability; D018510:RNA, Helminth / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; C410586:LIN-41 protein, C elegans; D018510:RNA, Helminth; D012333:RNA, Messenger; D014157:Transcription Factors
keywords: 3′ UTR; 5′ UTR; EGR; RNA-binding protein; heterochronic; mRNA degradation; positional effect; ribosome profiling; stem cell; translational repression