ArticleCell reports2022
A bidirectional competitive interaction between circHomer1 and Homer1b within the orbitofrontal cortex regulates reversal learning.
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Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33citing papers in PubMed
4.2field-weighted citation impact, top 4% of its field
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- A brain-enriched circRNA blood biomarker can predict response to SSRI antidepressants.Molecular psychiatry · 2026Article
- Prefrontal circHomer1 regulates synaptic and behavioral adaptations induced by cocaine.Molecular psychiatry · 2026Article
- Circular RNAs in metabolic health: bridging the gap between molecular biology and therapy.Cell death & disease · 2026Review
- Circular RNAScience advances · 2026Article
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- CircHomer1 may contribute to postoperative cognitive impairment by modulating Homer1b/mGluR5-associated signaling in the vCA1 region of aged mice.Frontiers in molecular neuroscience · 2026Article
- CircHOMER1 in mediating porcine skeletal muscle development.BMC genomics · 2025Article
- The noncoding circular RNAiScience · 2025Article
- Article
- Direct circRNA-mRNA Binding Controls mRNA Fate: A New Mechanism for circRNAs.Non-coding RNA · 2025Review
- Circular RNAs as a novel player in synaptic transmission and neuropsychiatric disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Function and Molecular Mechanism of Circhomer1 in Myogenesis.International journal of molecular sciences · 2025Article
- Opioid-Induced Regulation of Cortical Circular-International journal of molecular sciences · 2025Article
- Circular RNAs in neurological conditions - computational identification, functional validation, and potential clinical applications.Molecular psychiatry · 2025Review
- Formation of Circular RNAs.Advances in experimental medicine and biology · 2025Review
- Recent Advances in the Role of Non-coding RNAs in Fetal Alcohol Spectrum Disorders.Advances in experimental medicine and biology · 2025Review
- Biogenesis and function of circular RNAs and their implications in the Down syndrome brain.Frontiers in genetics · 2025Review
- Aberrant encoding of event saliency in the orbitofrontal cortex following loss of the psychiatric-associated circular RNA, circHomer1.Translational psychiatry · 2024Article
- Back to the Origin: Mechanisms of circRNA-Directed Regulation of Host Genes in Human Disease.Non-coding RNA · 2024Review
- Review
Corrections and comments
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Authors and funding
27 authors at 10 institutions in 3 countries.
Alexander K HafezDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Amber J ZimmermanDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Grigorios PapageorgiouDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Jayapriya ChandrasekaranDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Stephen K AmoahDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Rixing LinMcGill Group for Suicide Studies, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada.
Evelyn LozanoDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Caroline PierottiDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Michela Dell'OrcoDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Brigham J HartleyPamela Sklar Division of Psychiatric Genomics, Friedman Brain Institute, Departments of Genetics and Genomic Sciences, Neuroscience, and Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Begüm AluralCenter for Genomic Medicine, Chemical Neurobiology Laboratory, Departments of Neurology and Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Jasmin LalondeCenter for Genomic Medicine, Chemical Neurobiology Laboratory, Departments of Neurology and Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
John Matthew EspositoTranslational Neuroscience Laboratory, Mclean Hospital, Belmont, MA, USA.
Sabina BerrettaTranslational Neuroscience Laboratory, Mclean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Program in Neuroscience, Harvard Medical School, Boston, MA, USA.
Alessio SquassinaDepartment of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
Caterina ChillottiUnit of Clinical Pharmacology, University Hospital Agency of Cagliari, Cagliari, Italy.
Georgios VoloudakisPamela Sklar Division of Psychiatric Genomics, New York, NY, USA; Department of Genetics and Genomic Sciences, New York, NY, USA; Icahn Institute for Data Science and Genomic Technology, New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Zhiping ShaoPamela Sklar Division of Psychiatric Genomics, New York, NY, USA; Department of Genetics and Genomic Sciences, New York, NY, USA; Icahn Institute for Data Science and Genomic Technology, New York, NY, USA.
John F FullardPamela Sklar Division of Psychiatric Genomics, New York, NY, USA; Department of Genetics and Genomic Sciences, New York, NY, USA; Icahn Institute for Data Science and Genomic Technology, New York, NY, USA.
Kristen J BrennandPamela Sklar Division of Psychiatric Genomics, Friedman Brain Institute, Departments of Genetics and Genomic Sciences, Neuroscience, and Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Gustavo TureckiMcGill Group for Suicide Studies, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada.
Panos RoussosPamela Sklar Division of Psychiatric Genomics, New York, NY, USA; Department of Genetics and Genomic Sciences, New York, NY, USA; Icahn Institute for Data Science and Genomic Technology, New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Mental Illness Research, Education and Clinical Centers, James J. Peters VA Medical Center, Bronx, NY, USA.
Roy H PerlisHarvard Medical School, Department of Psychiatry, Boston, MA, USA; Center for Experimental Drugs and Diagnostics, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stephen J HaggartyCenter for Genomic Medicine, Chemical Neurobiology Laboratory, Departments of Neurology and Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Nora Perrone-BizzozeroDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Jonathan L BrigmanDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Nikolaos MelliosDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. Electronic address: nmellios@salud.unm.edu.
University of New Mexico · USMassachusetts General Hospital · USDouglas Mental Health University Institute · CAHarvard University · USIcahn School of Medicine at Mount Sinai · USPediatrics and Genetics · USAllen Institute for Brain Science · USJames J. Peters VA Medical Center · USMcLean Hospital · USUniversity of Cagliari · IT
Funding
Unfolded Protein Response and Autophagy in T Helper Cell Effector FunctionP20GM121176 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Monica Rosas Lemus · 2017 to 2026
$24.9MTranscranial Direct Current Stimulation for Treatment of Auditory Verbal HalluciP20GM103472 · NIGMS · THE MIND RESEARCH NETWORK · PI CALHOUN, VINCE D · 2012 to 2017
$14.3MUnderstanding the molecular mechanisms that contribute to neuropsychiatric symptoms in Alzheimer DiseaseR01AG067025 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FINKBEINER, STEVEN M, HAROUTUNIAN, VAHRAM · 2019 to 2023
$11.8MHigher Order Chromatin and Genetic Risk for Alzheimer's DiseaseR01AG050986 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2015 to 2025
$11.2MUnderstanding the protective and neuroinflammatory role of human brain immune cells in Alzheimer DiseaseR01AG065582 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAROUTUNIAN, VAHRAM, ROUSSOS, PANAGIOTIS · 2020 to 2024
$9.9MMolecular Profiling of SchizophreniaR01MH110921 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHESS, ANDREW J, ROUSSOS, PANAGIOTIS · 2016 to 2020
$6.9MHigher Order Chromatin and Genetic Risk for SchizophreniaR01MH106056 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, BRENNAND, KRISTEN JENNIFER · 2015 to 2023
$6.7MThe 3D genome in transcriptional regulation across the postnatal life span, with implications for schizophrenia and bipolar disorderU01MH116442 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, DRACHEVA, STELLA · 2018 to 2022
$5.9MMultiethnic genomic epigenomic and transcriptomic fine-mapping and functional validation analysis of schizophrenia and bipolar disorder risk lociR01MH125246 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2021 to 2025
$5.0MAlcohol Research Training in NeurosciencesT32AA014127 · NIAAA · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Jonathan L Brigman · 2003 to 2026
$3.3MIntegrated Multiscale Networks in SchizophreniaR01MH109897 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BRENNAND, KRISTEN JENNIFER, ROUSSOS, PANAGIOTIS · 2016 to 2020
$3.0MContrasting causal microRNAs in forebrain and midbrain COS hiPSC neural cellsR01MH101454 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BRENNAND, KRISTEN JENNIFER · 2013 to 2017
$2.8MBLRD VA I01 BX002395NIAAA NIH HHS R01 AA025652NIAAA NIH HHS R01 AA026583NIAAA NIH HHS T32 AA014127NIA NIH HHS R01 AG050986NIA NIH HHS R01 AG065582NIA NIH HHS R01 AG067025NIGMS NIH HHS P20 GM103472NIGMS NIH HHS P20 GM121176NIMH NIH HHS F31 MH122121NIMH NIH HHS R01 MH101454NIMH NIH HHS R01 MH106056NIMH NIH HHS R01 MH109897NIMH NIH HHS R01 MH110921NIMH NIH HHS R01 MH125246NIMH NIH HHS R01 MH125899NIMH NIH HHS R33 MH087896NIMH NIH HHS R56 MH119150NIMH NIH HHS U01 MH116442
Abstract
Although circular RNAs (circRNAs) are enriched in the brain, their relevance for brain function and psychiatric disorders is poorly understood. Here, we show that circHomer1 is inversely associated with relative HOMER1B mRNA isoform levels in both the orbitofrontal cortex (OFC) and stem-cell-derived neuronal cultures of subjects with psychiatric disorders. We further demonstrate that in vivo circHomer1 knockdown (KD) within the OFC can inhibit the synaptic expression of Homer1b mRNA. Furthermore, we show that circHomer1 directly binds to Homer1b mRNA and that Homer1b-specific KD increases synaptic circHomer1 levels and improves OFC-mediated behavioral flexibility. Importantly, double circHomer1 and Homer1b in vivo co-KD results in a complete rescue in circHomer1-associated alterations in both chance reversal learning and synaptic gene expression. Lastly, we uncover an RNA-binding protein that can directly bind to circHomer1 and promote its biogenesis. Taken together, our data provide mechanistic insights into the importance of circRNAs in brain function and disease.
Indexed as
AnimalsBipolar DisorderGene Expression RegulationGene Knockdown TechniquesHomer Scaffolding ProteinsHumansMaleMiceMice, Inbred C57BLPrefrontal CortexReversal LearningRNA, CircularHomer Scaffolding ProteinsRNA, Circularbipolar disordercircHomer1circRNAscognitive flexibilityHomer1OFCreversal learning
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