Widespread RNA editing dysregulation in brains from autistic individuals
Transcriptomic analyses of postmortem brains have begun to elucidate molecular abnormalities in autism spectrum disorder (ASD). However, a crucial pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled global patterns of adenosine-to-...
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| Veröffentlicht in: | Nature neuroscience 2019-01, Vol.22 (1), p.25-36 |
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| creator | Tran, Stephen S. Jun, Hyun-Ik Bahn, Jae Hoon Azghadi, Adel Ramaswami, Gokul Van Nostrand, Eric L. Nguyen, Thai B. Hsiao, Yun-Hua E. Lee, Changhoon Pratt, Gabriel A. Martínez-Cerdeño, Verónica Hagerman, Randi J. Yeo, Gene W. Geschwind, Daniel H. Xiao, Xinshu |
| description | Transcriptomic analyses of postmortem brains have begun to elucidate molecular abnormalities in autism spectrum disorder (ASD). However, a crucial pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled global patterns of adenosine-to-inosine (A-to-I) editing in a large cohort of postmortem brains of people with ASD. We observed a global bias for hypoediting in ASD brains, which was shared across brain regions and involved many synaptic genes. We show that the Fragile X proteins FMRP and FXR1P interact with RNA-editing enzymes (ADAR proteins) and modulate A-to-I editing. Furthermore, we observed convergent patterns of RNA-editing alterations in ASD and Fragile X syndrome, establishing this as a molecular link between these related diseases. Our findings, which are corroborated across multiple data sets, including dup15q (genomic duplication of 15q11.2-13.1) cases associated with intellectual disability, highlight RNA-editing dysregulation in ASD and reveal new mechanisms underlying this disorder.
An overall downregulation of RNA editing was observed in postmortem brains from people with autism, which was consistent across brain regions and genetic disorder subtypes. These changes were regulated by the RNA-binding proteins FMRP and FXR1P. |
| doi_str_mv | 10.1038/s41593-018-0287-x |
| format | Article |
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An overall downregulation of RNA editing was observed in postmortem brains from people with autism, which was consistent across brain regions and genetic disorder subtypes. These changes were regulated by the RNA-binding proteins FMRP and FXR1P.</description><identifier>ISSN: 1097-6256</identifier><identifier>EISSN: 1546-1726</identifier><identifier>DOI: 10.1038/s41593-018-0287-x</identifier><identifier>PMID: 30559470</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>38 ; 38/91 ; 45 ; 631/114/2114 ; 631/337/1645/1944 ; 692/699/476/1373 ; Abnormalities ; Adenosine ; Adenosine Deaminase - genetics ; Adenosine Deaminase - metabolism ; Animal Genetics and Genomics ; Autism ; Autistic Disorder - genetics ; Autistic Disorder - metabolism ; Autistic persons ; Behavioral Sciences ; Binding proteins ; Biological Techniques ; Biomedical and Life Sciences ; Biomedicine ; Brain ; Brain - metabolism ; Brain research ; Editing ; Enzymes ; Fragile X Mental Retardation Protein - genetics ; Fragile X Mental Retardation Protein - metabolism ; Fragile X syndrome ; Gene Expression Profiling ; Genes ; Genetic aspects ; Genetic disorders ; Genetic research ; Genomes ; Genomics ; Health aspects ; Humans ; Intellectual disabilities ; Medical research ; Neurobiology ; Neurons - metabolism ; Neurosciences ; Pervasive developmental disorders ; Physiological aspects ; Protein binding ; Proteins ; Ribonucleic acid ; RNA ; RNA Editing ; RNA processing ; RNA-Binding Proteins - genetics ; RNA-Binding Proteins - metabolism ; Synaptogenesis</subject><ispartof>Nature neuroscience, 2019-01, Vol.22 (1), p.25-36</ispartof><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2018</rights><rights>COPYRIGHT 2019 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jan 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c571t-e702e6bf74cbe8d4d6e3a54cc77c5dfdcb7d7ec4208a8c6bd914576d5f9ef80b3</citedby><cites>FETCH-LOGICAL-c571t-e702e6bf74cbe8d4d6e3a54cc77c5dfdcb7d7ec4208a8c6bd914576d5f9ef80b3</cites><orcidid>0000-0002-9362-8029 ; 0000-0002-5188-0082 ; 0000-0003-2896-3450</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41593-018-0287-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41593-018-0287-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30559470$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tran, Stephen S.</creatorcontrib><creatorcontrib>Jun, Hyun-Ik</creatorcontrib><creatorcontrib>Bahn, Jae Hoon</creatorcontrib><creatorcontrib>Azghadi, Adel</creatorcontrib><creatorcontrib>Ramaswami, Gokul</creatorcontrib><creatorcontrib>Van Nostrand, Eric L.</creatorcontrib><creatorcontrib>Nguyen, Thai B.</creatorcontrib><creatorcontrib>Hsiao, Yun-Hua E.</creatorcontrib><creatorcontrib>Lee, Changhoon</creatorcontrib><creatorcontrib>Pratt, Gabriel A.</creatorcontrib><creatorcontrib>Martínez-Cerdeño, Verónica</creatorcontrib><creatorcontrib>Hagerman, Randi J.</creatorcontrib><creatorcontrib>Yeo, Gene W.</creatorcontrib><creatorcontrib>Geschwind, Daniel H.</creatorcontrib><creatorcontrib>Xiao, Xinshu</creatorcontrib><title>Widespread RNA editing dysregulation in brains from autistic individuals</title><title>Nature neuroscience</title><addtitle>Nat Neurosci</addtitle><addtitle>Nat Neurosci</addtitle><description>Transcriptomic analyses of postmortem brains have begun to elucidate molecular abnormalities in autism spectrum disorder (ASD). However, a crucial pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled global patterns of adenosine-to-inosine (A-to-I) editing in a large cohort of postmortem brains of people with ASD. We observed a global bias for hypoediting in ASD brains, which was shared across brain regions and involved many synaptic genes. We show that the Fragile X proteins FMRP and FXR1P interact with RNA-editing enzymes (ADAR proteins) and modulate A-to-I editing. Furthermore, we observed convergent patterns of RNA-editing alterations in ASD and Fragile X syndrome, establishing this as a molecular link between these related diseases. Our findings, which are corroborated across multiple data sets, including dup15q (genomic duplication of 15q11.2-13.1) cases associated with intellectual disability, highlight RNA-editing dysregulation in ASD and reveal new mechanisms underlying this disorder.
An overall downregulation of RNA editing was observed in postmortem brains from people with autism, which was consistent across brain regions and genetic disorder subtypes. 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However, a crucial pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled global patterns of adenosine-to-inosine (A-to-I) editing in a large cohort of postmortem brains of people with ASD. We observed a global bias for hypoediting in ASD brains, which was shared across brain regions and involved many synaptic genes. We show that the Fragile X proteins FMRP and FXR1P interact with RNA-editing enzymes (ADAR proteins) and modulate A-to-I editing. Furthermore, we observed convergent patterns of RNA-editing alterations in ASD and Fragile X syndrome, establishing this as a molecular link between these related diseases. Our findings, which are corroborated across multiple data sets, including dup15q (genomic duplication of 15q11.2-13.1) cases associated with intellectual disability, highlight RNA-editing dysregulation in ASD and reveal new mechanisms underlying this disorder.
An overall downregulation of RNA editing was observed in postmortem brains from people with autism, which was consistent across brain regions and genetic disorder subtypes. These changes were regulated by the RNA-binding proteins FMRP and FXR1P.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>30559470</pmid><doi>10.1038/s41593-018-0287-x</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-9362-8029</orcidid><orcidid>https://orcid.org/0000-0002-5188-0082</orcidid><orcidid>https://orcid.org/0000-0003-2896-3450</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1097-6256 |
| ispartof | Nature neuroscience, 2019-01, Vol.22 (1), p.25-36 |
| issn | 1097-6256 1546-1726 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6375307 |
| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | 38 38/91 45 631/114/2114 631/337/1645/1944 692/699/476/1373 Abnormalities Adenosine Adenosine Deaminase - genetics Adenosine Deaminase - metabolism Animal Genetics and Genomics Autism Autistic Disorder - genetics Autistic Disorder - metabolism Autistic persons Behavioral Sciences Binding proteins Biological Techniques Biomedical and Life Sciences Biomedicine Brain Brain - metabolism Brain research Editing Enzymes Fragile X Mental Retardation Protein - genetics Fragile X Mental Retardation Protein - metabolism Fragile X syndrome Gene Expression Profiling Genes Genetic aspects Genetic disorders Genetic research Genomes Genomics Health aspects Humans Intellectual disabilities Medical research Neurobiology Neurons - metabolism Neurosciences Pervasive developmental disorders Physiological aspects Protein binding Proteins Ribonucleic acid RNA RNA Editing RNA processing RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism Synaptogenesis |
| title | Widespread RNA editing dysregulation in brains from autistic individuals |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T21%3A18%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Widespread%20RNA%20editing%20dysregulation%20in%20brains%20from%20autistic%20individuals&rft.jtitle=Nature%20neuroscience&rft.au=Tran,%20Stephen%20S.&rft.date=2019-01-01&rft.volume=22&rft.issue=1&rft.spage=25&rft.epage=36&rft.pages=25-36&rft.issn=1097-6256&rft.eissn=1546-1726&rft_id=info:doi/10.1038/s41593-018-0287-x&rft_dat=%3Cgale_pubme%3EA573339738%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2157866374&rft_id=info:pmid/30559470&rft_galeid=A573339738&rfr_iscdi=true |