Journal article
Dynamic landscape and regulation of RNA editing in mammals
MH Tan, Q Li, R Shanmugam, R Piskol, J Kohler, AN Young, KI Liu, R Zhang, G Ramaswami, K Ariyoshi, A Gupte, LP Keegan, CX George, A Ramu, N Huang, EA Pollina, DS Leeman, A Rustighi, YPS Goh, F Aguet Show all
Nature | NATURE PORTFOLIO | Published : 2017
DOI: 10.1038/nature24041
Abstract
Adenosine-to-inosine (A-to-I) RNA editing is a conserved posttranscriptional mechanism mediated by ADAR enzymes that diversifies the transcriptome by altering selected nucleotides in RNA molecules1. Although many editing sites have recently been discovered2-7, the extent to which most sites are edited and how the editing is regulated in different biological contexts are not fully understood8-10. 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 primat..
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Funding Acknowledgements
We thank C. Mason and L. Pipes for help with nonhuman primate RNA-seq data, Y. Hu, P Sahbaie, A. Chang, K. McGowan and R. Hannibal for technical assistance, and J. Baker and H. H. Ng for use of laboratory resources. We also thank A. Fire, Y. Wan, K. W. K. Sung, W. Zhai, S. Prabhakar,and members of the Li and Tan laboratories for discussions and critical reading of the manuscript. This work is supported by National Institutes of Health (NIH) grants R01GM102484, R01GM124215 and U01HG007593 (J.B.L.), R01GM040536 (K.N.), R01CA175058 (K.N.), and R01A1012520 (C.E.S.), Ellison Medical Foundation (J.B.L. and K. N.), Stanford University Department of Genetics (J.B.L.), Genome Institute of Singapore (M.H.T.), Nanyang Technological University School of Chemical and Biomedical Engineering (M.H.T), National Medical Research Council OFIRG15nov151 (M.H.T), the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health (K.N.), MRC and European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement No 621368 (M.A.O'C.), NHMRC project grant 1102006 (C.W. and J.B.L.), Italian Health Ministry (RF-2011-02346976) and the Italian Association for Cancer Research (AIRC) Special Program Molecular Clinical Oncology '5 per mille' (grant no. 10016), AIRC IG (grant no. 17659) (G.D.S.), the Cariplo Foundation (grant no. 2014-0812) (G.D.S.), Stanford Graduate Fellowship (G.R.), German Academic Exchange Service research fellowship (R. P.) and Stanford University School of Medicine Dean's Fellowship (Q.L., R.P. and R.Z.). The Genotype-Tissue Expression (GTEx) project was supported by the Common Fund of the Office of the Director of the NIH. Additional funds were provided by the NCI, NHGRI, NHLBI, NIDA, NIMH and NINDS. Donors were enrolled at Biospecimen Source Sites funded by NCI\SAIC-Frederick, Inc. (SAIC-F) subcontracts to the National Disease Research Interchange (10XS170), Roswell Park Cancer Institute (10XS171), and Science Care, Inc. (X10S172). The Laboratory, Data Analysis, and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to The Broad Institute, Inc. Biorepository operations were funded through an SAIC-F subcontract to Van Andel Institute (10ST1035). Additional data repository and project management were provided by SAIC-F (HHSN261200800001E). The Brain Bank was supported by a supplement to University of Miami grants DA006227 and DA033684 and to contract NO1MH000028. Statistical Methods development grants were made to the University of Geneva (MH090941 and MH101814), the University of Chicago (MH090951, MH090937, MH101320 and MH101825), the University of North Carolina-Chapel Hill (MH090936 and MH101819), Harvard University (MH090948), Stanford University (MH101782), Washington University St Louis (MH101810), and the University of Pennsylvania (MH101822).