{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:04:45Z","timestamp":1791475485675,"version":"4.3.4"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T00:00:00Z","timestamp":1704240000000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>MicroRNAs have emerged as important regulators of the gene expression landscape in temporal lobe epilepsy. The mechanisms that control microRNA levels and influence target choice remain, however, poorly understood. RNA editing is a post-transcriptional mechanism mediated by the adenosine acting on RNA (ADAR) family of proteins that introduces base modification that diversifies the gene expression landscape. RNA editing has been studied for the mRNA landscape but the extent to which microRNA editing occurs in human temporal lobe epilepsy is unknown. Here, we used small RNA-sequencing data to characterize the identity and extent of microRNA editing in human temporal lobe epilepsy brain samples. This detected low-to-high editing in over 40 of the identified microRNAs. Among microRNA exhibiting the highest editing was miR-376a-3p, which was edited in the seed region and this was predicted to significantly change the target pool. The edited form was expressed at lower levels in human temporal lobe epilepsy samples. We modelled the shift in editing levels of miR-376a-3p in human-induced pluripotent stem cell-derived neurons. Reducing levels of the edited form of miR-376a-3p using antisense oligonucleotides resulted in extensive gene expression changes, including upregulation of mitochondrial and metabolism-associated pathways. Together, these results show that differential editing of microRNAs may re-direct targeting and result in altered functions relevant to the pathophysiology of temporal lobe epilepsy and perhaps other disorders of neuronal hyperexcitability.<\/jats:p>","DOI":"10.1093\/braincomms\/fcad355","type":"journal-article","created":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T09:30:16Z","timestamp":1704274216000},"source":"Crossref","is-referenced-by-count":4,"title":["Differential microRNA editing may drive target pathway switching in human temporal lobe epilepsy"],"prefix":"10.1093","volume":"6","author":[{"given":"Kelvin E How","family":"Lau","sequence":"first","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"},{"name":"FutureNeuro SFI Research Centre, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc T","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"},{"name":"FutureNeuro SFI Research Centre, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaideep C","family":"Kesavan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"},{"name":"FutureNeuro SFI Research Centre, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Langa","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"},{"name":"FutureNeuro SFI Research Centre, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Fanning","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"},{"name":"FutureNeuro SFI Research Centre, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary P","family":"Brennan","sequence":"additional","affiliation":[{"name":"FutureNeuro SFI Research Centre, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"},{"name":"UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin , Dublin 4 , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaya","family":"Sanz-Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"},{"name":"FutureNeuro SFI Research Centre, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Villegas-Salmer\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"},{"name":"FutureNeuro SFI Research Centre, Royal College of Surgeons in Ireland University of Medicine and Health Sciences , Dublin D02 YN77 , Ireland"},{"name":"The SFI Centre for Research Training in Genomics Data Science , University of Galway, Galway H91 TK33 , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yan","sequence":"additional","affiliation":[{"name":"Omiics ApS , 8200 Aarhus N , Denmark"},{"name":"Interdisciplinary Nanoscience Centre (iNANO), Department of Molecular Biology and Genetics, Aarhus University , Aarhus 8000 , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten T","family":"Ven\u00f8","sequence":"additional","affiliation":[{"name":"Omiics ApS , 8200 Aarhus N , Denmark"},{"name":"Interdisciplinary Nanoscience Centre (iNANO), Department of Molecular Biology and Genetics, Aarhus University , Aarhus 8000 , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D","family":"Mills","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy, Queen Square Institute of Neurology, University College London , London WC1N 3BG , United Kingdom"},{"name":"Chalfont Centre for Epilepsy , Chalfont St.Peter SL9 0RJ , UK"},{"name":"Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam , 1105 AZ Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3989-7471","authenticated-orcid":false,"given":"Felix","family":"Rosenow","sequence":"additional","affiliation":[{"name":"Goethe-University Frankfurt, Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, University Hospital, 60590 Frankfurt , Germany"},{"name":"Goethe-University Frankfurt, LOEWE Center for Personalized Translational Epilepsy Research (CePTER) , 60590 Frankfurt , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Bauer","sequence":"additional","affiliation":[{"name":"Goethe-University Frankfurt, Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, University Hospital , 60590 Frankfurt , Germany"},{"name":"Goethe-University Frankfurt, LOEWE Center for Personalized Translational Epilepsy Research (CePTER) , 60590 Frankfurt , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4128-9317","authenticated-orcid":false,"given":"J\u00f8rgen","family":"Kjems","sequence":"additional","affiliation":[{"name":"Interdisciplinary Nanoscience Centre (iNANO), Department of Molecular Biology and Genetics, Aarhus University , Aarhus 8000 , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C","family":"Henshall","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal 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