{"doi":"10.1016/j.jmb.2025.169534","title":"RNA Binding by the Yeast Slf1 and Sro9 La-motif Domains","abstract":"Slf1 and Sro9 are paralogous RNA-binding proteins in Saccharomyces cerevisiae that belong to the LARP1 (La-related protein 1) subgroup of the greater La family. These proteins function as translational regulators during cellular stress, acting through either direct mRNA binding or interactions with ribosomal factors. In this study, we characterized the structural and RNA-binding properties of the La-motif (LaM) domains of Slf1 and Sro9 using a combination of nuclear magnetic resonance (NMR) spectroscopy, calorimetry, and molecular dynamics (MD) simulations. Both LaM domains exhibited micromolar affinity for RNA ligands, including poly(A). Notably, the Sro9 LaM domain displayed a thermal denaturation midpoint of 36 °C suggesting a potential regulatory mechanism for this protein during hyperthermic stress. An NMR analysis of the Slf1 LaM domain revealed that its RNA binding platform undergoes widespread conformational sampling on the micro- to millisecond timescale, even in the presence of RNA. Molecular dynamics simulations corroborated these experimental NMR observations and highlighted the role of transient aromatic stacking during RNA binding. Furthermore, a glutamine substitution mutant (Q278A in Slf1) known to impair RNA binding also destabilized the protein-RNA interaction in molecular simulations. Collectively, our findings confirm that RNA binding by LaM domains is an evolutionarily conserved feature among eukaryotes and provide critical insights into the structural and dynamic mechanisms underlying Slf1 and Sro9 function in yeast.","journal":"Journal of Molecular Biology","year":2025,"id":580703,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9631,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1229486,"name":"Aron A. Shoara","orcid":"0000-0002-5580-1273","position":1,"is_corresponding":false},{"id":1491852,"name":"Logan W. Donaldson","orcid":"0000-0001-5034-2699","position":2,"is_corresponding":false},{"id":1491851,"name":"Eduardo Garcia Pacheco","orcid":"0009-0003-8393-3200","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T02:58:43.046112Z","pmid":"41223936","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":[]}