title: dTIS11 Protein-dependent polysomal deadenylation is the key step in AU-rich element-mediated mRNA decay in Drosophila cells.
abstract: The destabilization of AU-rich element (ARE)-containing mRNAs mediated by proteins of the TIS11 family is conserved among eukaryotes including Drosophila. Previous studies have demonstrated that Tristetraprolin, a human protein of the TIS11 family, induces the degradation of ARE-containing mRNAs through a large variety of mechanisms including deadenylation, decapping, and P-body targeting. We have previously shown that the degradation of the mRNA encoding the antimicrobial peptide Cecropin A1 (CecA1) is controlled by the TIS11 protein (dTIS11) in Drosophila cells. In this study, we used CecA1 mRNA as a model to investigate the molecular mechanism of dTIS11-mediated mRNA decay. We observed that during the biphasic deadenylation and decay process of this mRNA, dTIS11 enhances deadenylation performed by the CCR4-CAF-NOT complex while the mRNA is still associated with ribosomes. Sequencing of mRNA degradation intermediates revealed that the complete deadenylation of the mRNA triggers its decapping and decay in both the 5'-3' and the 3'-5' directions. Contrary to the observations made for its mammalian homologs, overexpression of dTIS11 does not promote the localization of ARE-containing mRNAs in P-bodies but rather decreases the accumulation of CecA1 mRNA in these structures by enhancing the degradation process. Therefore, our results suggest that proteins of the TIS11 family may have acquired additional functions in the course of evolution from invertebrates to mammals.
authors.affiliation: Laboratoire de Biologie Moléculaire du Gène, Université Libre de Bruxelles, 12 rue Pr. Jeener et Brachet, 6041 Gosselies, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Vindry
authors.affiliation: Laboratoire de Biologie Moléculaire du Gène, Université Libre de Bruxelles, 12 rue Pr. Jeener et Brachet, 6041 Gosselies, Belgium.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Lauwers
authors.affiliation: Laboratoire d'Immunobiologie, Université Libre de Bruxelles, 12 rue Pr. Jeener et Brachet, 6041 Gosselies, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Hutin
authors.affiliation: Laboratoire de Biologie Moléculaire du Gène, Université Libre de Bruxelles, 12 rue Pr. Jeener et Brachet, 6041 Gosselies, Belgium.
authors.forename: Romuald
authors.initials: R
authors.lastname: Soin
authors.affiliation: Laboratoire de Biologie Moléculaire du Gène, Université Libre de Bruxelles, 12 rue Pr. Jeener et Brachet, 6041 Gosselies, Belgium.
authors.forename: Corinne
authors.initials: C
authors.lastname: Wauquier
authors.affiliation: Laboratoire de Biologie Moléculaire du Gène, Université Libre de Bruxelles, 12 rue Pr. Jeener et Brachet, 6041 Gosselies, Belgium; Center for Microscopy and Molecular Imaging, Faculté des Sciences, Université Libre de Bruxelles, 12 rue Pr. Jeener et Brachet, 6041 Gosselies, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Kruys
authors.affiliation: Laboratoire de Biologie Moléculaire du Gène, Université Libre de Bruxelles, 12 rue Pr. Jeener et Brachet, 6041 Gosselies, Belgium. Electronic address: cgueydan@ulb.ac.be.
authors.forename: Cyril
authors.initials: C
authors.lastname: Gueydan
mesh_terms: D063307:AU Rich Elements / Q000502:physiology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D019143:Evolution, Molecular; D006801:Humans; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; D029721:Drosophila Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C572932:Tis11 protein, Drosophila; D051816:Tristetraprolin; C497552:ZFP36 protein, human; C031161:cecropin A; C501437:CCR4 protein, Drosophila; D012260:Ribonucleases