{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Thapa BV"],"funding":["NIH","NIH HHS","NIGMS NIH HHS"],"pagination":["jkaf298"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12869082"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(2)"],"pubmed_abstract":["Aminoacyl-tRNA synthetases (aaRSs) are essential for translation, as they charge tRNA molecules with their corresponding amino acids. Alterations in aaRSs can significantly disrupt both cytosolic and mitochondrial translation. Through a forward genetic screen for mitochondrial unfolded protein response (UPRmt) activators in Caenorhabditis elegans, we identified a missense mutation (P447V) in the previously uncharacterized gene Y105E8A.20, which encodes for a methionine tRNA synthetase (MetRS). Here, we characterize the UPRmt induction by Y105E8A.20, which we call mars-2, and demonstrate that the P447V allele is a loss-of-function mutation. Furthermore, we show that impaired mars-2 activity leads to reduced mitochondrial-encoded protein abundance, depletion of mitochondrial membrane potential, fragmented mitochondrial morphology, and mild developmental delay, although the animals remain viable. Hence, this hypomorphic mars-2(P447V) strain provides a valuable tool for studying mitochondrial translation and understanding how aaRSs are involved in mitochondrial homeostasis."],"journal":["G3 (Bethesda, Md.)"],"pubmed_title":["Identification of an uncharacterized gene as a mitochondrial methionine tRNA synthetase in Caenorhabditis elegans."],"pmcid":["PMC12869082"],"funding_grant_id":["R35GM145378","P40 OD010440","R35 GM145378"],"pubmed_authors":["Thapa BV","Taylor DI","Patel MR","Held JP","Das M"],"additional_accession":[]},"is_claimable":false,"name":"Identification of an uncharacterized gene as a mitochondrial methionine tRNA synthetase in Caenorhabditis elegans.","description":"Aminoacyl-tRNA synthetases (aaRSs) are essential for translation, as they charge tRNA molecules with their corresponding amino acids. Alterations in aaRSs can significantly disrupt both cytosolic and mitochondrial translation. Through a forward genetic screen for mitochondrial unfolded protein response (UPRmt) activators in Caenorhabditis elegans, we identified a missense mutation (P447V) in the previously uncharacterized gene Y105E8A.20, which encodes for a methionine tRNA synthetase (MetRS). Here, we characterize the UPRmt induction by Y105E8A.20, which we call mars-2, and demonstrate that the P447V allele is a loss-of-function mutation. Furthermore, we show that impaired mars-2 activity leads to reduced mitochondrial-encoded protein abundance, depletion of mitochondrial membrane potential, fragmented mitochondrial morphology, and mild developmental delay, although the animals remain viable. Hence, this hypomorphic mars-2(P447V) strain provides a valuable tool for studying mitochondrial translation and understanding how aaRSs are involved in mitochondrial homeostasis.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-07-02T03:10:05.802Z","creation":"2026-07-02T03:08:45.29Z"},"accession":"S-EPMC12869082","cross_references":{"pubmed":["41359510"],"doi":["10.1093/g3journal/jkaf298"]}}