{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Green KM"],"funding":["BLRD VA","Veterans Affairs","NINDS NIH HHS","National Institutes of Health","Cellular and Molecular Biology Graduate Program at the University of Michigan","NIGMS NIH HHS"],"pagination":["2521-2534"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9618161"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31(15)"],"pubmed_abstract":["Repeat-associated non-AUG (RAN) translation of expanded repeat-mutation mRNA produces toxic peptides in neurons of patients suffering from neurodegenerative diseases. Recent findings indicate that RAN translation in diverse model systems is not inhibited by cellular stressors that impair global translation through phosphorylation of the alpha subunit of eIF2, the essential eukaryotic translation initiation factor that brings the initiator tRNA to the 40S ribosome. Using in vitro, cell-based and Drosophila models, we examined the role of alternative ternary complex factors that may function in place of eIF2, including eIF2A, eIF2D, DENR and MCTS1. Among these factors, DENR knockdown had the greatest inhibitory effect on RAN translation of expanded GGGGCC and CGG repeat reporters and its red"],"journal":["Human molecular genetics"],"pubmed_title":["Non-canonical initiation factors modulate repeat-associated non-AUG translation."],"pmcid":["PMC9618161"],"funding_grant_id":["F31NS100302","R01 NS099280","F31 NS127371","I01 BX004842","P50HD104463","R01NS099280","R01NS086810","T32 GM145470","T32GM007315","BX004842"],"pubmed_authors":["Miller SL","Todd PK","Green KM","Malik I"],"additional_accession":[]},"is_claimable":false,"name":"Non-canonical initiation factors modulate repeat-associated non-AUG translation.","description":"Repeat-associated non-AUG (RAN) translation of expanded repeat-mutation mRNA produces toxic peptides in neurons of patients suffering from neurodegenerative diseases. Recent findings indicate that RAN translation in diverse model systems is not inhibited by cellular stressors that impair global translation through phosphorylation of the alpha subunit of eIF2, the essential eukaryotic translation initiation factor that brings the initiator tRNA to the 40S ribosome. Using in vitro, cell-based and Drosophila models, we examined the role of alternative ternary complex factors that may function in place of eIF2, including eIF2A, eIF2D, DENR and MCTS1. Among these factors, DENR knockdown had the greatest inhibitory effect on RAN translation of expanded GGGGCC and CGG repeat reporters and its red","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Aug","modification":"2025-04-19T00:57:45.7Z","creation":"2025-04-07T11:57:07.578Z"},"accession":"S-EPMC9618161","cross_references":{"pubmed":["35220421"],"doi":["10.1093/hmg/ddac021"]}}