{"doi":"10.1101/2022.02.25.480133","title":"Deficiency of the RNA-binding protein Cth2 extends yeast replicative lifespan by alleviating its repressive effects on mitochondrial function","abstract":"Abstract Iron dyshomeostasis contributes to aging, but little information is available about the molecular mechanisms. Here, we provide evidence that, in Saccharomyces cerevisiae , aging is associated with altered expression of genes involved in iron homeostasis. We further demonstrate that defects in the conserved mRNA-binding protein Cth2, which controls stability and translation of mRNAs encoding iron-containing proteins, increase lifespan by alleviating its repressive effects on mitochondrial function. Mutation of the conserved cysteine residue in Cth2 that inhibits its RNA-binding activity is sufficient to confer longevity, whereas Cth2 gain-of-function shortens replicative lifespan. Consistent with its function in RNA degradation, we demonstrate that Cth2 deficiency relieves Cth2-mediated post-transcriptional repression of nuclear-encoded components of the electron transport chain. Our findings uncover a major role of the RNA-binding protein Cth2 in the regulation of lifespan and suggest that modulation of iron starvation signaling can serve as a target for potential aging interventions.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298576,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":910495,"name":"Carine Beaupère","orcid":"0000-0002-7220-4892","position":1,"is_corresponding":false},{"id":910496,"name":"Hanna Barlit","orcid":"0000-0002-7334-2525","position":2,"is_corresponding":false},{"id":910497,"name":"Antonia María Romero","orcid":"0000-0002-2727-279X","position":3,"is_corresponding":false},{"id":468640,"name":"Mitsuhiro Tsuchiya","orcid":null,"position":4,"is_corresponding":false},{"id":910498,"name":"Michael Muir","orcid":"0000-0001-5596-3443","position":5,"is_corresponding":false},{"id":910499,"name":"María Teresa Martínez‐Pastor","orcid":"0000-0002-4128-958X","position":6,"is_corresponding":false},{"id":910500,"name":"Sergi Puig","orcid":"0000-0002-1856-490X","position":7,"is_corresponding":false},{"id":287812,"name":"Matt Kaeberlein","orcid":"0000-0002-1311-3421","position":8,"is_corresponding":false},{"id":910501,"name":"Vyacheslav M. Labunskyy","orcid":"0000-0001-9317-1076","position":9,"is_corresponding":false},{"id":910494,"name":"Praveen K. Patnaik","orcid":"0000-0002-7260-4052","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T00:31:36.269611Z","pmid":null,"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":[]}