Faculty Opinions recommendation of Dynamic landscape and regulation of RNA editing in mammals.
Year: 2018
Type: peer-review
Abstract: Adenosine-to-inosine (A-to-I) RNA editing is a conserved post-transcriptional mechanism mediated by ADAR enzymes that diversifies the transcriptome by altering selected nucleotides in RNA molecules 1 .Although many editing sites have recently been discovered 2-7 , the extent to which most sites are edited and how the editing is regulated in different biological contexts are not fully understood [8][9][10] .Here we report dynamic spatiotemporal patterns and new regulators of RNA editing, discovered through an extensive profiling of A-to-I RNA editing in 8,551 human samples (representing 53 body sites from 552 individuals) from the Genotype-Tissue Expression (GTEx) project and in hundreds of other primate and mouse samples.We show that editing levels in nonrepetitive coding regions vary more between tissues than editing levels in repetitive regions.Globally, ADAR1 is the primary editor of repetitive sites and ADAR2 is the primary editor of nonrepetitive coding sites, whereas the catalytically inactive ADAR3 predominantly acts as an inhibitor of editing.Cross-species analysis of RNA editing in several tissues revealed that species, rather than tissue type, is the primary determinant of editing levels, suggesting stronger cisdirected regulation of RNA editing for most sites, although the small set of conserved coding sites is under stronger trans-regulation.In addition, we curated an extensive set of ADAR1 and ADAR2 targets and showed that many editing sites display distinct tissue-specific regulation by the ADAR enzymes in vivo.Further analysis of the GTEx data revealed several potential regulators of editing, such as AIMP2, which reduces editing in muscles by enhancing the degradation of the ADAR proteins.Collectively, our work provides insights into the complex cis-and trans-regulation of Ato-I editing.The prevalence and importance of A-to-I RNA editing have been illuminated in recent years largely owing to the rapid adoption of high-throughput sequencing technologies 11,12 .Separate laboratories have examined the RNA editome across many tissues or developmental stages in human and other mammals [13][14][15][16][17] .However, the published studies are limited in the number of samples and tissues examined and do not systematically compare
Author: Tony D Southall
Institution: Imperial College London
Language: English
Topic: RNA regulation and disease
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Ellison Medical Foundation, Pennsylvania Department of Health, University of Miami, University of Pennsylvania, Harvard University, University of Chicago, Broad Institute, European Commission, Nanyang Technological University, Deutscher Akademischer Austauschdienst, Fondazione Cariplo, Associazione Italiana per la Ricerca sul Cancro, Genome Institute of Singapore, Université de Genève, National Institutes of Health, School of Medicine, Stanford University, Medical Research Council, National Health and Medical Research Council, National Medical Research Council, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, NIH Office of the Director, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, Common Fund
Awards: Methods for high-resolution analysis of genetic effects on gene expression, G1206703408, G1217436835, The ERA Chair Culture as a Catalyst to Maximize the Potential of CEITEC, G1534570039, G1561323845, G1650773652, Identification and validation of cell specific eQTLs by Bayesian modeling, G1883398070, Using the Transcriptome for SNP and Gene Annotation, Why does endogenous RNA need A-to-I editing?, G2158443041, G2180054251, G2651523388, G2835668146, G2877753951, G3221727586, G32319252, Epigenetic Marks of Cocaine Addiction, G3387558946, G3443372292, G347407575, G3503792436, G3547560438, G3793778294, G386607036, G4124418613, Systems approaches to link tissue-specific expression to disease, Harnessing GTEx to Create Transcriptome Knowledge and Inform Disease Biology, G4478373029, G4606556408, G4715193760, G4729234894, G4959535594, HIGH RESOLUTION ALLELE SPECIFIC EXPRESSION ASSAYS, G563538711, G5737582129, Statistical analysis of gene expression quantitative trait loci (eQTL), G6314915104, G6317516893, G634178657, Profiling and Dissecting the Dynamic Regulation of RNA Editing, G7075004892, G7274654584, G7353525908, G7665525972, G7761642487, G7924626839, G7953026188, G7958282288, G8644024335, Regulation of R-loop Formation and Genome Stability by ADAR1, G8719970897, G8788848806, G8906494432
OpenAlex ID: W4239508778