ArticleCell reports2022
Spatiotemporal and genetic regulation of A-to-I editing throughout human brain development.
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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 25 papers.
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25citing papers in PubMed
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Who cites it
25 citing papers in PubMed.
- Spatial transcriptomics reveals laminar and cell-type-specific A-to-I RNA editing signatures in the macaque cortex.Nature communications · 2026Article
- Accurate prediction in reconstructed spatial transcriptomes does not ensure valid biological discovery.bioRxiv : the preprint server for biology · 2026Article
- Trisomy 21 Drives ADARB1 Overexpression and Premature RNA Recoding in the Developing Fetal Brain.Nature communications · 2026Article
- Multi-Tissue Genetic Regulation of RNA Editing in Pigs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genetic Association and Functional Prediction of PTEN and TSC1 3'UTR Variants in Autism Spectrum Disorder Among Tunisian Patients.Molecular neurobiology · 2025Article
- RNA modifications in health and disease: from mechanistic insights to therapeutic applications.Precision clinical medicine · 2025Review
- RNA modifications, alternative splicing and circular RNA landscape in the mouse brain: inosine and beyond.Scientific reports · 2025Article
- Meta-analysis of genetic regulation of RNA editing in the human brain identifies new genes underlying neurological disease.medRxiv : the preprint server for health sciences · 2025Article
- Roles of RNA modifications in aging and age-related diseases.BMB reports · 2025Review
- DEAD/DEAH-box RNA helicases shape the risk of neurodevelopmental disorders.Trends in genetics : TIG · 2025Review
- PRMT5 promotes full-length HTT expression by repressing multiple proximal intronic polyadenylation sites.Nucleic acids research · 2025Article
- EndoVIA for quantifying A-to-I editing and mapping the subcellular localization of edited transcripts.Methods in enzymology · 2025Article
- Charting and probing the activity of ADARs in human development and cell-fate specification.Nature communications · 2024Article
- Genetics of cell-type-specific post-transcriptional gene regulation during human neurogenesis.American journal of human genetics · 2024Article
- ADAR1 prevents ZBP1-dependent PANoptosis via A-to-I RNA editing in developmental sevoflurane neurotoxicity.Cell biology and toxicology · 2024Article
- Divergent landscapes of A-to-I editing in postmortem and living human brain.Nature communications · 2024Article
- Divergent landscapes of A-to-I editing in postmortem and living human brain.medRxiv : the preprint server for health sciences · 2024Article
- Temporal landscape and translational regulation of A-to-I RNA editing in mouse retina development.BMC biology · 2024Article
- ADAR Family Proteins: A Structural Review.Current issues in molecular biology · 2024Review
- RNA editing enzymes: structure, biological functions and applications.Cell & bioscience · 2024Review
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Authors and funding
16 authors.
Winston H DredgeSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Xuanjia FanSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Laura SloofmanSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Lindsay LiangDepartment of Psychiatry and Behavioral Sciences and UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Enrico MossottoSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Kendall MooreSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sarah ZipkowitzSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Minghui WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Genomics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Bin ZhangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Genomics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
Jiebiao WangDepartment of Biostatistics, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, USA.
Nenad SestanDepartment of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Program in Cellular Neuroscience, Neurodegeneration, and Repair and Yale Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Comparative Medicine, Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, CT 06510, USA.
Bernie DevlinDepartment of Psychiatry, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213, USA.
Kathryn RoederCarnegie Mellon University, Statistics & Data Science Department, Pittsburgh, PA 15213, USA.
Stephan J SandersDepartment of Psychiatry and Behavioral Sciences and UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Joseph D BuxbaumSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Michael S BreenSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: michael.breen@mssm.edu.
Funding
Integrative Network Biology Approaches to Identify, Characterize and Validate Molecular Subtypes in Alzheimer's DiseaseU01AG046170 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WANG, MINGHUI, ZHANG, BIN · 2013 to 2022
$26.0MIdentification and characterization of AD risk networks using multi-dimensional "omics" dataU01AG052411 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CRUCHAGA, CARLOS, GOATE, ALISON M · 2016 to 2020
$4.5MSYSTEMATIC DRUG REPURPOSING TARGETING IMMUNE ACTIVATION NETWORKS IN ALZHEIMER'S DISEASE (AD)RF1AG059319 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, GANDY, SAMUEL E. · 2018 to 2018
$4.2MLarge-scale reprogramming and expression analysis of patient-derived neural cells in schizophreniaR01MH111679 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BRENNAND, KRISTEN JENNIFER, BUXBAUM, JOSEPH D. · 2017 to 2021
$4.0MMethods for single-cell CRISPR screens and multiomic data: constructing powerful well-calibrated tests, circumventing unmeasured confounding, and accounting for denoising and imputationR01MH123184 · NIMH · CARNEGIE-MELLON UNIVERSITY · PI KATHRYN M ROEDER · 2020 to 2026
$3.8MTowards a comprehensive signaling pathway map of parahippocampal vulnerability in Alzheimers DiseaseRF1AG057440 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAROUTUNIAN, VAHRAM, NOGGLE, SCOTT ALLEN · 2017 to 2017
$3.5M1/4 - The Autism Sequencing Consortium: Discovering autism risk genes and how they impact core features of the disorderR01MH129724 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Joseph D. Buxbaum · 2022 to 2026
$2.0M3/4 The Autism Sequencing Consortium: Discovering autism risk genes and how they impact core features of the disorderR01MH129725 · NIMH · CARNEGIE-MELLON UNIVERSITY · PI KATHRYN M ROEDER · 2022 to 2026
$1.9M1/2 Identification and Validation of Expression Quantitative Trait Loci (eQTLs) in discrete cell types across human brain developmentU01MH122678 · NIMH · YALE UNIVERSITY · PI SESTAN, NENAD · 2021 to 2022
$1.4MNIA NIH HHS RF1 AG057440NIA NIH HHS RF1 AG059319NIA NIH HHS U01 AG046170NIA NIH HHS U01 AG052411NIMH NIH HHS R01 MH111679NIMH NIH HHS R01 MH123184NIMH NIH HHS R01 MH129724NIMH NIH HHS R01 MH129725NIMH NIH HHS U01 MH122678
Abstract
Posttranscriptional RNA modifications by adenosine-to-inosine (A-to-I) editing are abundant in the brain, yet elucidating functional sites remains challenging. To bridge this gap, we investigate spatiotemporal and genetically regulated A-to-I editing sites across prenatal and postnatal stages of human brain development. More than 10,000 spatiotemporally regulated A-to-I sites were identified that occur predominately in 3' UTRs and introns, as well as 37 sites that recode amino acids in protein coding regions with precise changes in editing levels across development. Hyper-edited transcripts are also enriched in the aging brain and stabilize RNA secondary structures. These features are conserved in murine and non-human primate models of neurodevelopment. Finally, thousands of cis-editing quantitative trait loci (edQTLs) were identified with unique regulatory effects during prenatal and postnatal development. Collectively, this work offers a resolved atlas linking spatiotemporal variation in editing levels to genetic regulatory effects throughout distinct stages of brain maturation.
Indexed as
InosineRNA Editing3' Untranslated RegionsAdenosineAdenosine DeaminaseAnimalsBrainHumansMicePrimates3' Untranslated RegionsAdenosineAdenosine DeaminaseInosinebrain maturationCP: Molecular biologyCP: NeuroscienceedQTLshyper-editinglate-fetal transitionRNA modificationsRNA recoding
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