{"doi":"10.1016/j.cub.2024.04.079","title":"CMTR-1 RNA methyltransferase mutations activate widespread expression of a dopaminergic neuron-specific mitochondrial complex I gene","abstract":"The mitochondrial proteome is comprised of approximately 1,100 proteins, 1 all but 12 of which are encoded by the nuclear genome in C. elegans . The expression of nuclear-encoded mitochondrial proteins varies widely across cell lineages and metabolic states, 2 , 3 , 4 but the factors that specify these programs are not known. Here, we identify mutations in two nuclear-localized mRNA processing proteins, CMTR1/CMTR-1 and SRRT/ARS2/SRRT-1, which we show act via the same mechanism to rescue the mitochondrial complex I mutant NDUFS2/gas-1(fc21) . CMTR-1 is an FtsJ-family RNA methyltransferase that, in mammals, 2′- O -methylates the first nucleotide 3′ to the mRNA CAP to promote RNA stability and translation 5 , 6 , 7 , 8 . The mutations isolated in cmtr-1 are dominant and lie exclusively in the regulatory G-patch domain. SRRT-1 is an RNA binding partner of the nuclear cap-binding complex and determines mRNA transcript fate. 9 We show that cmtr-1 and srrt-1 mutations activate embryonic expression of NDUFS2/ nduf-2. 2, a paralog of NDUFS2/ gas-1 normally expressed only in dopaminergic neurons, and that nduf-2.2 is necessary for the complex I rescue by the cmtr-1 G-patch mutant. Additionally, we find that loss of the cmtr-1 G-patch domain cause ectopic localization of CMTR-1 protein to processing bodies (P bodies), phase-separated organelles involved in mRNA storage and decay. 10 P-body localization of the G-patch mutant CMTR-1 contributes to the rescue of the hyperoxia sensitivity of the NDUFS2/gas-1 mutant. This study suggests that mRNA methylation at P bodies may control nduf-2.2 gene expression, with broader implications for how the mitochondrial proteome is translationally remodeled in the face of tissue-specific metabolic requirements and stress.","journal":"Current Biology","year":2024,"id":463284,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1212004,"name":"Presli P. Wiesenthal","orcid":"0000-0002-7757-6652","position":1,"is_corresponding":false},{"id":31806,"name":"Vamsi K. Mootha","orcid":"0000-0001-9924-642X","position":2,"is_corresponding":false},{"id":25406,"name":"Gary Ruvkun","orcid":"0000-0002-7473-8484","position":3,"is_corresponding":false},{"id":105016,"name":"Joshua D. Meisel","orcid":"0000-0002-6944-5177","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:04:28.838123Z","pmid":"38810637","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}