title: Identification and characterization of novel factors that act in the nonsense-mediated mRNA decay pathway in nematodes, flies and mammals.
abstract: Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNAs harboring premature termination codons (PTCs). We have conducted a genome-wide RNAi screen in Caenorhabditis elegans that resulted in the identification of five novel NMD genes that are conserved throughout evolution. Two of their human homologs, GNL2 (ngp-1) and SEC13 (npp-20), are also required for NMD in human cells. We also show that the C. elegans gene noah-2, which is present in Drosophila melanogaster but absent in humans, is an NMD factor in fruit flies. Altogether, these data identify novel NMD factors that are conserved throughout evolution, highlighting the complexity of the NMD pathway and suggesting that yet uncovered novel factors may act to regulate this process.
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital University of Edinburgh, Edinburgh, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Casadio
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital University of Edinburgh, Edinburgh, UK Dasa.Longman@igmm.ed.ac.uk Javier.Caceres@igmm.ed.ac.uk.
authors.forename: Dasa
authors.initials: D
authors.lastname: Longman
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital University of Edinburgh, Edinburgh, UK.
authors.forename: Nele
authors.initials: N
authors.lastname: Hug
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital University of Edinburgh, Edinburgh, UK.
authors.forename: Laurent
authors.initials: L
authors.lastname: Delavaine
authors.affiliation: School of Life Sciences, University of Sussex, Brighton, UK.
authors.forename: Raúl
authors.initials: R
authors.lastname: Vallejos Baier
authors.affiliation: School of Life Sciences, University of Sussex, Brighton, UK.
authors.forename: Claudio R
authors.initials: CR
authors.lastname: Alonso
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital University of Edinburgh, Edinburgh, UK Dasa.Longman@igmm.ed.ac.uk Javier.Caceres@igmm.ed.ac.uk.
authors.forename: Javier F
authors.initials: JF
authors.lastname: Cáceres
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D004527:Egg Proteins / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian; D019143:Evolution, Molecular; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D059365:Nonsense Mediated mRNA Decay / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D004527:Egg Proteins; D008840:Microfilament Proteins; C560800:Mon2 protein, Drosophila; C104699:NGP-1 antigen, human; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C507456:SEC13 protein, human; C515801:SMG5 protein, human; C423085:nompA protein, Drosophila; D019204:GTP-Binding Proteins
keywords: C. elegans; RNAi screen; nonsense‐mediated decay; smg genes