{"doi":"10.1016/j.celrep.2023.113662","title":"TDP-43 chronic deficiency leads to dysregulation of transposable elements and gene expression by affecting R-loop and 5hmC crosstalk","abstract":"TDP-43 is an RNA/DNA-binding protein that forms aggregates in various brain disorders. TDP-43 engages in many aspects of RNA metabolism, but its molecular roles in regulating genes and transposable elements (TEs) have not been extensively explored. Chronic TDP-43 knockdown impairs cell proliferation and cellular responses to DNA damage. At the molecular level, TDP-43 chronic deficiency affects gene expression either locally or distally by concomitantly altering the crosstalk between R-loops and 5-hydroxymethylcytosine (5hmC) in gene bodies and long-range enhancer/promoter interactions. Furthermore, TDP-43 knockdown induces substantial disease-relevant TE activation by influencing their R-loop and 5hmC homeostasis in a locus-specific manner. Together, our findings highlight the genomic roles of TDP-43 in modulating R-loop-5hmC coordination in coding genes, distal regulatory elements, and TEs, presenting a general and broad molecular mechanism underlying the contributions of proteinopathies to the etiology of neurodegenerative disorders.","journal":"Cell Reports","year":2024,"id":425845,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":620456,"name":"Yangping Li","orcid":"0009-0003-9631-3828","position":1,"is_corresponding":false},{"id":568545,"name":"Jian‐Feng Xiang","orcid":"0000-0001-5181-1645","position":2,"is_corresponding":false},{"id":618516,"name":"Kedamawit Tilahun","orcid":"0000-0003-2107-1580","position":3,"is_corresponding":false},{"id":1224129,"name":"Jie Jiang","orcid":"0009-0007-3377-3033","position":4,"is_corresponding":false},{"id":295693,"name":"Victor G. Corces","orcid":"0000-0001-5140-4337","position":5,"is_corresponding":false},{"id":888285,"name":"Bing Yao","orcid":"0000-0002-3205-8130","position":6,"is_corresponding":false},{"id":1169035,"name":"Yingzi Hou","orcid":"0000-0002-7729-0515","position":0,"is_corresponding":true}],"reference_count":132,"raw_metadata":null,"created_at":"2026-07-19T01:58:32.160975Z","pmid":"38184854","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":[]}