{"doi":"10.1101/2025.11.16.688537","title":"Mechanism of Ribosome Stalling by the AMD1 C-terminal Tail Arrest Peptide","abstract":"Abstract AMD1 encodes Adenosylmethionine decarboxylase 1 (AMD1), a key enzyme required for polyamine biosynthesis. A subset of ribosomes translating the AMD1 coding sequence (CDS) read through the stop codon and pause at the next in-frame stop codon 384 nucleotides downstream. The resulting C-terminal extension (C-tail) is universally conserved across all vertebrates, implying that its molecular function is critical to their fitness. Despite growing evidence that such cis-acting elements regulate translation of their genes, the molecular mechanism by which the C-tail mediates ribosome stalling remains unclear. Here, we determined the structure of the ribosome nascent chain complex paused by the AMD1 C-tail which traps eukaryotic release factor 1 (eRF1) with the ATP-binding cassette sub-family E member 1 (ABCE1). The nascent chain forms a molecular clamp that positions an arginine finger in the peptidyl-transferase center, occluding the accommodation of the eRF1 GGQ motif thereby hampering translation termination. Analysis of aggregated ribosome profiling data revealed several genes with a pattern of stop codon readthrough followed by ribosome stalling at a specific location, suggesting that regulatory readthrough-stall mechanisms may not be limited to AMD1 .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":581821,"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":0.9534,"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":1493718,"name":"Fabio S. Boiocchi","orcid":null,"position":1,"is_corresponding":false},{"id":17784,"name":"Michał I. Świrski","orcid":"0000-0002-8585-136X","position":2,"is_corresponding":false},{"id":1493719,"name":"Kyle A. Meiklejohn","orcid":null,"position":3,"is_corresponding":false},{"id":17895,"name":"Martina M. Yordanova","orcid":"0000-0001-9693-3857","position":4,"is_corresponding":false},{"id":17938,"name":"Pavel V. Baranov","orcid":"0000-0001-9017-0270","position":5,"is_corresponding":false},{"id":17834,"name":"Ahmad Jomaa","orcid":"0000-0002-5543-7942","position":6,"is_corresponding":false},{"id":1323390,"name":"Emir Maldosevic","orcid":"0000-0001-6796-3053","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:58:51.328454Z","pmid":"41292971","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":[]}