{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Anderson R"],"funding":["NIA NIH HHS","NIGMS NIH HHS"],"pagination":["702-714.e10"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10923110"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["84(4)"],"pubmed_abstract":["Expansions of CAG trinucleotide repeats cause several rare neurodegenerative diseases. The disease-causing repeats are translated in multiple reading frames and without an identifiable initiation codon. The molecular mechanism of this repeat-associated non-AUG (RAN) translation is not known. We find that expanded CAG repeats create new splice acceptor sites. Splicing of proximal donors to the repeats produces unexpected repeat-containing transcripts. Upon splicing, depending on the sequences surrounding the donor, CAG repeats may become embedded in AUG-initiated open reading frames. Canonical AUG-initiated translation of these aberrant RNAs may account for proteins that have been attributed to RAN translation. Disruption of the relevant splice donors or the in-frame AUG initiation codons is sufficient to abrogate RAN translation. Our findings provide a molecular explanation for the abnormal translation products observed in CAG trinucleotide repeat expansion disorders and add to the repertoire of mechanisms by which repeat expansion mutations disrupt cellular functions."],"journal":["Molecular cell"],"pubmed_title":["CAG repeat expansions create splicing acceptor sites and produce aberrant repeat-containing RNAs."],"pmcid":["PMC10923110"],"funding_grant_id":["R00 AG053434","R35 GM151111"],"pubmed_authors":["Jain A","Farenhem K","Anderson R","Das MR","Chang Y","Schmitz CO"],"additional_accession":[]},"is_claimable":false,"name":"CAG repeat expansions create splicing acceptor sites and produce aberrant repeat-containing RNAs.","description":"Expansions of CAG trinucleotide repeats cause several rare neurodegenerative diseases. The disease-causing repeats are translated in multiple reading frames and without an identifiable initiation codon. The molecular mechanism of this repeat-associated non-AUG (RAN) translation is not known. We find that expanded CAG repeats create new splice acceptor sites. Splicing of proximal donors to the repeats produces unexpected repeat-containing transcripts. Upon splicing, depending on the sequences surrounding the donor, CAG repeats may become embedded in AUG-initiated open reading frames. Canonical AUG-initiated translation of these aberrant RNAs may account for proteins that have been attributed to RAN translation. Disruption of the relevant splice donors or the in-frame AUG initiation codons is sufficient to abrogate RAN translation. Our findings provide a molecular explanation for the abnormal translation products observed in CAG trinucleotide repeat expansion disorders and add to the repertoire of mechanisms by which repeat expansion mutations disrupt cellular functions.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-06-02T01:55:25.897Z","creation":"2025-04-04T02:12:39.433Z"},"accession":"S-EPMC10923110","cross_references":{"pubmed":["38295802"],"doi":["10.1016/j.molcel.2024.01.006"]}}