{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kriachkov V"],"funding":["Victorian Cancer Agency","National Health and Medical Research Council","Australian Research Council"],"pagination":["102774"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9830226"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["299(1)"],"pubmed_abstract":["Hexanucleotide expansion mutations in C9ORF72 are a frequent cause of amyotrophic lateral sclerosis. We previously reported that long arginine-rich dipeptide repeats (DPRs), mimicking abnormal proteins expressed from the hexanucleotide expansion, caused translation stalling when expressed in cell culture models. Whether this stalling provides a mechanism of pathogenicity remains to be determined. Here, we explored the molecular features of DPR-induced stalling and examined whether known mechanisms such as ribosome quality control (RQC) regulate translation elongation on sequences that encode arginine-rich DPRs. We demonstrate that arginine-rich DPRs lead to stalling in a length-dependent manner, with lengths longer than 40 repeats invoking severe translation arrest. Mutational screening of"],"journal":["The Journal of biological chemistry"],"pubmed_title":["Arginine-rich C9ORF72 ALS proteins stall ribosomes in a manner distinct from a canonical ribosome-associated quality control substrate."],"pmcid":["PMC9830226"],"funding_grant_id":["DP170103093","MCRF16007","APP1161803"],"pubmed_authors":["McWilliam HEG","Ormsby AR","Mintern JD","Kriachkov V","Hatters DM","Furic L","Kusnadi EP","Ritchie ME","Amarasinghe SL"],"additional_accession":[]},"is_claimable":false,"name":"Arginine-rich C9ORF72 ALS proteins stall ribosomes in a manner distinct from a canonical ribosome-associated quality control substrate.","description":"Hexanucleotide expansion mutations in C9ORF72 are a frequent cause of amyotrophic lateral sclerosis. We previously reported that long arginine-rich dipeptide repeats (DPRs), mimicking abnormal proteins expressed from the hexanucleotide expansion, caused translation stalling when expressed in cell culture models. Whether this stalling provides a mechanism of pathogenicity remains to be determined. Here, we explored the molecular features of DPR-induced stalling and examined whether known mechanisms such as ribosome quality control (RQC) regulate translation elongation on sequences that encode arginine-rich DPRs. We demonstrate that arginine-rich DPRs lead to stalling in a length-dependent manner, with lengths longer than 40 repeats invoking severe translation arrest. Mutational screening of","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-05-27T23:13:53.847Z","creation":"2024-12-04T12:35:10.499Z"},"accession":"S-EPMC9830226","cross_references":{"pubmed":["36481270"],"doi":["10.1016/j.jbc.2022.102774"]}}