{"doi":"10.1002/advs.202004515","title":"Downregulation of a Dorsal Root Ganglion‐Specifically Enriched Long Noncoding RNA is Required for Neuropathic Pain by Negatively Regulating RALY‐Triggered Ehmt2 Expression","abstract":"Nerve injury-induced maladaptive changes of gene expression in dorsal root ganglion (DRG) neurons contribute to neuropathic pain. Long non-coding RNAs (lncRNAs) are emerging as key regulators of gene expression. Here, a conserved lncRNA is reported, named DRG-specifically enriched lncRNA (DS-lncRNA) for its high expression in DRG neurons. Peripheral nerve injury downregulates DS-lncRNA in injured DRG due, in part, to silencing of POU domain, class 4, transcription factor 3, a transcription factor that interacts with the DS-lncRNA gene promoter. Rescuing DS-lncRNA downregulation blocks nerve injury-induced increases in the transcriptional cofactor RALY-triggered DRG Ehmt2 mRNA and its encoding G9a protein, reverses the G9a-controlled downregulation of opioid receptors and Kcna2 in injured DRG, and attenuates nerve injury-induced pain hypersensitivities in male mice. Conversely, DS-lncRNA downregulation increases RALY-triggered Ehmt2/G9a expression and correspondingly decreases opioid receptor and Kcna2 expression in DRG, leading to neuropathic pain symptoms in male mice in the absence of nerve injury. Mechanistically, downregulated DS-lncRNA promotes more binding of increased RALY to RNA polymerase II and the Ehmt2 gene promoter and enhances Ehmt2 transcription in injured DRG. Thus, downregulation of DS-lncRNA likely contributes to neuropathic pain by negatively regulating the expression of RALY-triggered Ehmt2/G9a, a key neuropathic pain player, in DRG neurons.","journal":"Advanced Science","year":2021,"id":153205,"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":70,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"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":290418,"name":"Shibin Du","orcid":null,"position":1,"is_corresponding":false},{"id":649999,"name":"Kun Wang","orcid":"0000-0003-1396-6325","position":2,"is_corresponding":false},{"id":289054,"name":"Xinying Guo","orcid":"0000-0002-8428-5036","position":3,"is_corresponding":false},{"id":457004,"name":"Qingxiang Mao","orcid":"0000-0002-9268-4846","position":4,"is_corresponding":false},{"id":650000,"name":"Xiaozhou Feng","orcid":"0000-0002-2963-0546","position":5,"is_corresponding":false},{"id":211000,"name":"Lina Huang","orcid":null,"position":6,"is_corresponding":false},{"id":289055,"name":"Shaogen Wu","orcid":"0000-0001-5653-3357","position":7,"is_corresponding":false},{"id":650741,"name":"Bailing Hou","orcid":null,"position":8,"is_corresponding":false},{"id":289059,"name":"Yun‐Juan Chang","orcid":"0000-0003-2688-6391","position":9,"is_corresponding":false},{"id":650001,"name":"Tong Liu","orcid":"0000-0001-9234-1328","position":10,"is_corresponding":false},{"id":650002,"name":"Tong Chen","orcid":"0000-0002-2456-7170","position":11,"is_corresponding":false},{"id":298613,"name":"Hong Li","orcid":"0000-0001-5731-5335","position":12,"is_corresponding":false},{"id":457006,"name":"Thomas Bachmann","orcid":"0000-0003-2579-0400","position":13,"is_corresponding":false},{"id":414501,"name":"Alex Bekker","orcid":"0000-0002-6785-6714","position":14,"is_corresponding":false},{"id":477205,"name":"Huijuan Hu","orcid":"0000-0003-2306-2514","position":15,"is_corresponding":false},{"id":289060,"name":"Yuan‐Xiang Tao","orcid":"0000-0003-1777-3272","position":16,"is_corresponding":false},{"id":649998,"name":"Zhiqiang Pan","orcid":"0000-0002-7520-5129","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T23:43:39.820288Z","pmid":"34383386","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":[]}