Caenorhabditis elegans glp-4 Encodes a Valyl Aminoacyl tRNA Synthetase

摘要

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 was identified by the temperature-sensitive allele 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 encodes a valyl aminoacyl transfer RNA synthetase () and that the probable null phenotype is early larval lethality. Phenotypic analysis indicates () is partial loss of function in the soma. Structural modeling suggests that 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 () 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. () 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 () mutants are the result of germline deficiency or reduced translation.