Dynamic landscape and regulation of RNA editing in mammals

J 2017

Dynamic landscape and regulation of RNA editing in mammals

TAN, M.H.; Q. LI; R. SHANMUGAM; R. PISKOL; J. KOHLER et al.

Základní údaje

Originální název

Dynamic landscape and regulation of RNA editing in mammals

Autoři

Vydání

Nature, LONDON, NATURE PUBLISHING GROUP, 2017, 0028-0836

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 41.577

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/17:00100306

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

SEQUENCING DATA; ACCURATE IDENTIFICATION; CELL-DIFFERENTIATION; BRAIN-DEVELOPMENT; SITES; GENE; TRANSCRIPTOME; GENOME; ADAR1; DEAMINASE

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 12. 3. 2018 11:14, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Aden osine-to-inosine (A-to-I) RNA editing is a conserved post transcriptional mechanism mediated by ADAR enzymes that diversities 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(8-10). 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 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.

Návaznosti

621368, interní kód MU

Název: The ERA Chair Culture as a Catalyst to Maximize the Potential of CEITEC (Akronym: CEITEC_ERA)

Investor: Evropská unie, The ERA Chair Culture as a Catalyst to Maximize the Potential of CEITEC, Kapacity

Citovat

TAN, M.H.; Q. LI; R. SHANMUGAM; R. PISKOL; J. KOHLER; A.N. YOUNG; K.I. LIU; R. ZHANG; G.R. AMASWAMI; K. ARIYOSHI; A. GUPTE; Liam KEEGAN; C.X. GEORGE; A.R. AMU; N. HUANG; E.A. POLLINA; D.S. LEEMAN; A.R. USTIGHI; Y.P.S. GOH; A.C. HAWLA; Sal G. DEL; G. PELTZ; A.B. RUNET; D.F.C. ONRAD; C.E. SAMUEL; Mary Anne O'CONNELL; C.R. WALKLEY; K. NISHIKURA a J.B. LI. Dynamic landscape and regulation of RNA editing in mammals. Nature. LONDON: NATURE PUBLISHING GROUP, 2017, roč. 550, č. 7675, s. 249-272. ISSN 0028-0836. Dostupné z: https://doi.org/10.1038/nature24041.

@article{1410892,
   author = {Tan, M.H. and Li, Q. and Shanmugam, R. and Piskol, R. and Kohler, J. and Young, A.N. and Liu, K.I. and Zhang, R. and Amaswami, G.R. and Ariyoshi, K. and Gupte, A. and Keegan, Liam and George, C.X. and Amu, A.R. and Huang, N. and Pollina, E.A. and Leeman, D.S. and Ustighi, A.R. and Goh, Y.P.S. and Hawla, A.C. and Del, Sal G. and Peltz, G. and Runet, A.B. and Onrad, D.F.C. and Samuel, C.E. and O'Connell, Mary Anne and Walkley, C.R. and Nishikura, K. and Li, J.B.},
   article_location = {LONDON},
   article_number = {7675},
   doi = {https://doi.org/10.1038/nature24041},
   keywords = {SEQUENCING DATA; ACCURATE IDENTIFICATION; CELL-DIFFERENTIATION; BRAIN-DEVELOPMENT; SITES; GENE; TRANSCRIPTOME; GENOME; ADAR1; DEAMINASE},
   language = {eng},
   issn = {0028-0836},
   journal = {Nature},
   title = {Dynamic landscape and regulation of RNA editing in mammals},
   url = {https://www.nature.com/articles/nature24041.pdf},
   volume = {550},
   year = {2017}
}

TY  - JOUR
ID  - 1410892
AU  - Tan, M.H. - Li, Q. - Shanmugam, R. - Piskol, R. - Kohler, J. - Young, A.N. - Liu, K.I. - Zhang, R. - Amaswami, G.R. - Ariyoshi, K. - Gupte, A. - Keegan, Liam - George, C.X. - Amu, A.R. - Huang, N. - Pollina, E.A. - Leeman, D.S. - Ustighi, A.R. - Goh, Y.P.S. - Hawla, A.C. - Del, Sal G. - Peltz, G. - Runet, A.B. - Onrad, D.F.C. - Samuel, C.E. - O'Connell, Mary Anne - Walkley, C.R. - Nishikura, K. - Li, J.B.
PY  - 2017
TI  - Dynamic landscape and regulation of RNA editing in mammals
JF  - Nature
VL  - 550
IS  - 7675
SP  - 249
EP  - 249
PB  - NATURE PUBLISHING GROUP
SN  - 00280836
KW  - SEQUENCING DATA
KW  - ACCURATE IDENTIFICATION
KW  - CELL-DIFFERENTIATION
KW  - BRAIN-DEVELOPMENT
KW  - SITES
KW  - GENE
KW  - TRANSCRIPTOME
KW  - GENOME
KW  - ADAR1
KW  - DEAMINASE
UR  - https://www.nature.com/articles/nature24041.pdf
L2  - https://www.nature.com/articles/nature24041.pdf
N2  - Aden osine-to-inosine (A-to-I) RNA editing is a conserved post transcriptional mechanism mediated by ADAR enzymes that diversities 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(8-10). 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 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.
ER  -

TAN, M.H.; Q. LI; R. SHANMUGAM; R. PISKOL; J. KOHLER; A.N. YOUNG; K.I. LIU; R. ZHANG; G.R. AMASWAMI; K. ARIYOSHI; A. GUPTE; Liam KEEGAN; C.X. GEORGE; A.R. AMU; N. HUANG; E.A. POLLINA; D.S. LEEMAN; A.R. USTIGHI; Y.P.S. GOH; A.C. HAWLA; Sal G. DEL; G. PELTZ; A.B. RUNET; D.F.C. ONRAD; C.E. SAMUEL; Mary Anne O'CONNELL; C.R. WALKLEY; K. NISHIKURA a J.B. LI. Dynamic landscape and regulation of RNA editing in mammals. \textit{Nature}. LONDON: NATURE PUBLISHING GROUP, 2017, roč.~550, č.~7675, s.~249-272. ISSN~0028-0836. Dostupné z: https://doi.org/10.1038/nature24041.

Přehled o publikaci