{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Yang S"],"funding":["NIGMS NIH HHS"],"pubmed_abstract":["A nucleotide repeat expansion (NRE) in the first annotated intron of the <i>C9ORF72</i> gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While C9 NRE-containing RNAs can be translated into several toxic dipeptide repeat proteins, how an intronic NRE can assess the translation machinery in the cytoplasm remains unclear. By capturing and sequencing NRE-containing RNAs from patient-derived cells, we found that C9 NRE was exonized by the usage of downstream 5' splice sites and exported from the nucleus in a variety of spliced mRNA isoforms. <i>C9ORF72</i> aberrant splicing was substantially elevated in both C9 NRE<sup>+</sup> motor neurons and human brain tissues. Furthermore, NREs above the pathological threshold were sufficient t"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2023.11.13.566896"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10680656"],"repository":["biostudies-literature"],"pubmed_title":["Aberrant splicing exonizes &lt;i&gt;C9ORF72&lt;/i&gt; repeat expansion in ALS/FTD."],"pmcid":["PMC10680656"],"funding_grant_id":["DP2 GM132930","R35 GM152208"],"pubmed_authors":["Gendron TF","Guo JU","Veire AM","Pereira JD","Agrawal M","Sheth U","Yang S","Salgado JMS","Wijegunawardana D","Zhou J"],"additional_accession":[]},"is_claimable":false,"name":"Aberrant splicing exonizes &lt;i&gt;C9ORF72&lt;/i&gt; repeat expansion in ALS/FTD.","description":"A nucleotide repeat expansion (NRE) in the first annotated intron of the <i>C9ORF72</i> gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While C9 NRE-containing RNAs can be translated into several toxic dipeptide repeat proteins, how an intronic NRE can assess the translation machinery in the cytoplasm remains unclear. By capturing and sequencing NRE-containing RNAs from patient-derived cells, we found that C9 NRE was exonized by the usage of downstream 5' splice sites and exported from the nucleus in a variety of spliced mRNA isoforms. <i>C9ORF72</i> aberrant splicing was substantially elevated in both C9 NRE<sup>+</sup> motor neurons and human brain tissues. Furthermore, NREs above the pathological threshold were sufficient t","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Nov","modification":"2026-06-08T03:11:47.357Z","creation":"2026-06-08T03:08:28.002Z"},"accession":"S-EPMC10680656","cross_references":{"pubmed":["38014069"],"doi":["10.1101/2023.11.13.566896"]}}