{"doi":"10.1101/2021.04.25.441260","title":"The RNA helicase DHX36/G4R1 modulates <i>C9orf72</i> GGGGCC repeat-associated translation","abstract":"ABSTRACT GGGGCC (G 4 C 2 ) hexanucleotide repeat expansions (HRE) in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat-associated non-AUG (RAN) translation of this expansion generates toxic proteins that accumulate in patient brains and contribute to disease pathogenesis. The DEAH-Box Helicase 36 (DHX36/G4R1) plays active roles in RNA and DNA G-quadruplex (G4) resolution in cells. As G 4 C 2 repeats form G4 structures in vitro , we sought to determine the impact of manipulating DHX36 expression on repeat transcription and RAN translation. We found that DHX36 depletion suppresses RAN translation from reporter constructs in a repeat length dependent manner while overexpression of DHX36 enhances RAN translation from G 4 C 2 reporter RNAs. Taken together, these results suggest that DHX36 is active in regulating G 4 C 2 repeat translation, providing potential implications for therapeutic development in nucleotide repeats expansion disorders.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":215873,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":437786,"name":"Siara N. Sandwith","orcid":"0000-0002-2538-8772","position":1,"is_corresponding":false},{"id":658345,"name":"Katelyn M. Green","orcid":"0000-0001-5562-9920","position":2,"is_corresponding":false},{"id":438675,"name":"Antonio E. Chambers","orcid":null,"position":3,"is_corresponding":false},{"id":396461,"name":"Amy Krans","orcid":null,"position":4,"is_corresponding":false},{"id":422427,"name":"Heather M. Raimer","orcid":"0000-0002-7415-6011","position":5,"is_corresponding":false},{"id":659194,"name":"Meredith E. Sharlow","orcid":null,"position":6,"is_corresponding":false},{"id":437787,"name":"Michael Reisinger","orcid":"0000-0002-7939-0501","position":7,"is_corresponding":false},{"id":437785,"name":"Adam E. Richardson","orcid":"0009-0008-5395-8462","position":8,"is_corresponding":false},{"id":437788,"name":"Eric D. Routh","orcid":"0000-0002-7371-1802","position":9,"is_corresponding":false},{"id":438677,"name":"Melissa A. Smaldino","orcid":null,"position":10,"is_corresponding":false},{"id":422428,"name":"Yuh‐Hwa Wang","orcid":"0000-0002-9804-9368","position":11,"is_corresponding":false},{"id":438678,"name":"James P. Vaughn","orcid":null,"position":12,"is_corresponding":false},{"id":395497,"name":"Peter K. Todd","orcid":"0000-0003-4781-6376","position":13,"is_corresponding":false},{"id":437790,"name":"Philip J. Smaldino","orcid":"0000-0003-1855-5226","position":14,"is_corresponding":false},{"id":658344,"name":"Yi‐Ju Tseng","orcid":"0000-0002-2242-6200","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-18T23:53:00.192353Z","pmid":null,"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":[]}