title: Elimination of cap structures generated by mRNA decay involves the new scavenger mRNA decapping enzyme Aph1/FHIT together with DcpS.
abstract: Eukaryotic 5' mRNA cap structures participate to the post-transcriptional control of gene expression before being released by the two main mRNA decay pathways. In the 3'-5' pathway, the exosome generates free cap dinucleotides (m7GpppN) or capped oligoribonucleotides that are hydrolyzed by the Scavenger Decapping Enzyme (DcpS) forming m7GMP. In the 5'-3' pathway, the decapping enzyme Dcp2 generates m7GDP. We investigated the fate of m7GDP and m7GpppN produced by RNA decay in extracts and cells. This defined a pathway involving DcpS, NTPs and the nucleoside diphosphate kinase for m7GDP elimination. Interestingly, we identified and characterized in vitro and in vivo a new scavenger decapping enzyme involved in m7GpppN degradation. We show that activities mediating cap elimination identified in yeast are essentially conserved in human. Their alteration may contribute to pathologies, possibly through the interference of cap (di)nucleotide with cellular function.
authors.affiliation: Equipe Labellisée La Ligue, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre National de Recherche Scientifique (CNRS) UMR 7104/Institut National de Santé et de Recherche Médicale (INSERM) U964/Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Valerio
authors.initials: V
authors.lastname: Taverniti
authors.affiliation: Equipe Labellisée La Ligue, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre National de Recherche Scientifique (CNRS) UMR 7104/Institut National de Santé et de Recherche Médicale (INSERM) U964/Université de Strasbourg, 67404 Illkirch, France seraphin@igbmc.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Séraphin
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism; D012314:RNA Cap Analogs / Q000378:metabolism; D012315:RNA Caps / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D000255:Adenosine Triphosphate; D015226:Dinucleoside Phosphates; D004722:Endoribonucleases; D006153:Guanosine Diphosphate; D009699:N-Glycosyl Hydrolases; D009363:Neoplasm Proteins; D009701:Nucleoside-Diphosphate Kinase; D012314:RNA Cap Analogs; D012315:RNA Caps; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C017537:m(7)GMP; C111106:7-methylguanosine 5'-diphosphate; C062229:7-methyl-diguanosine triphosphate; C485332:DcpS protein, human; C478395:DCS1 protein, S cerevisiae