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. Although many editing sites have recently been discovered, the extent to which most sites are edited and how the editing is regulated in different biological contexts are not fully understood. 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 non-repetitive 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 non-repetitive 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 cis-directed 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 A-to-I editing.

• MeSH
• adenosindeaminasa * genetika   metabolismus   MeSH
• časoprostorová analýza MeSH
• druhová specificita MeSH
• editace RNA genetika   MeSH
• genotyp MeSH
• HEK293 buňky MeSH
• jaderné proteiny metabolismus   MeSH
• lidé MeSH
• myši MeSH
• orgánová specificita genetika   MeSH
• primáti genetika   MeSH
• proteiny vázající RNA * genetika   metabolismus   MeSH
• proteolýza MeSH
• svaly metabolismus   MeSH
• transkriptom genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• ADAR protein, human MeSH Prohlížeč
• ADAR1 protein, mouse MeSH Prohlížeč
• ADAR2 protein, mouse MeSH Prohlížeč
• ADARB1 protein, human MeSH Prohlížeč
• adenosindeaminasa * MeSH
• AIMP2 protein, human MeSH Prohlížeč
• jaderné proteiny MeSH
• proteiny vázající RNA * MeSH