title: Caenorhabditis elegans glp-4 Encodes a Valyl Aminoacyl tRNA Synthetase.
abstract: Germline stem cell proliferation is necessary to populate the germline with sufficient numbers of cells for gametogenesis and for signaling the soma to control organismal properties such as aging. The Caenorhabditis elegans gene glp-4 was identified by the temperature-sensitive allele bn2 where mutants raised at the restrictive temperature produce adults that are essentially germ cell deficient, containing only a small number of stem cells arrested in the mitotic cycle but otherwise have a morphologically normal soma. We determined that glp-4 encodes a valyl aminoacyl transfer RNA synthetase (VARS-2) and that the probable null phenotype is early larval lethality. Phenotypic analysis indicates glp-4(bn2ts) is partial loss of function in the soma. Structural modeling suggests that bn2 Gly296Asp results in partial loss of function by a novel mechanism: aspartate 296 in the editing pocket induces inappropriate deacylation of correctly charged Val-tRNA(val). Intragenic suppressor mutations are predicted to displace aspartate 296 so that it is less able to catalyze inappropriate deacylation. Thus glp-4(bn2ts) likely causes reduced protein translation due to decreased levels of Val-tRNA(val). The germline, as a reproductive preservation mechanism during unfavorable conditions, signals the soma for organismal aging, stress and pathogen resistance. glp-4(bn2ts) mutants are widely used to generate germline deficient mutants for organismal studies, under the assumption that the soma is unaffected. As reduced translation has also been demonstrated to alter organismal properties, it is unclear whether changes in aging, stress resistance, etc. observed in glp-4(bn2ts) mutants are the result of germline deficiency or reduced translation.
authors.affiliation: Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110.
authors.forename: Suchita
authors.initials: S
authors.lastname: Rastogi
authors.affiliation: Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110.
authors.forename: Ben
authors.initials: B
authors.lastname: Borgo
authors.affiliation: Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110.
authors.forename: Nanette
authors.initials: N
authors.lastname: Pazdernik
authors.affiliation: Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110.
authors.forename: Paul
authors.initials: P
authors.lastname: Fox
authors.affiliation: Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Mardis
authors.affiliation: National Institute of Genetics, Mishima, 411-8540 Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kohara
authors.affiliation: Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110.
authors.forename: Jim
authors.initials: J
authors.lastname: Havranek
authors.affiliation: Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110 ts@genetics.wustl.edu.
authors.forename: Tim
authors.initials: T
authors.lastname: Schedl
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000926:Anticodon; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D004789:Enzyme Activation; D056426:Genetic Loci; D005854:Germ Cells / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
chemical_list: D000926:Anticodon; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases
keywords: C. elegans; aging; germline; glp-4; stress resistance; valine-tRNA synthetase