ADAR-deficiency perturbs the global splicing landscape in mouse tissues.
Adenosine
/ chemistry
Adenosine Deaminase
/ genetics
Animals
Inosine
/ chemistry
Mice
Mice, Knockout
RNA Editing
/ genetics
RNA Processing, Post-Transcriptional
/ genetics
RNA Splicing
/ genetics
RNA, Circular
/ genetics
RNA, Messenger
/ genetics
RNA-Binding Proteins
/ genetics
Sequence Analysis, RNA
Journal
Genome research
ISSN: 1549-5469
Titre abrégé: Genome Res
Pays: United States
ID NLM: 9518021
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
09
09
2019
accepted:
10
07
2020
pubmed:
31
7
2020
medline:
11
11
2021
entrez:
31
7
2020
Statut:
ppublish
Résumé
Adenosine-to-inosine RNA editing and pre-mRNA splicing largely occur cotranscriptionally and influence each other. Here, we use mice deficient in either one of the two editing enzymes ADAR (ADAR1) or ADARB1 (ADAR2) to determine the transcriptome-wide impact of RNA editing on splicing across different tissues. We find that ADAR has a 100× higher impact on splicing than ADARB1, although both enzymes target a similar number of substrates with a large common overlap. Consistently, differentially spliced regions frequently harbor ADAR editing sites. Moreover, catalytically dead ADAR also impacts splicing, demonstrating that RNA binding of ADAR affects splicing. In contrast, ADARB1 editing sites are found enriched 5' of differentially spliced regions. Several of these ADARB1-mediated editing events change splice consensus sequences, therefore strongly influencing splicing of some mRNAs. A significant overlap between differentially edited and differentially spliced sites suggests evolutionary selection toward splicing being regulated by editing in a tissue-specific manner.
Identifiants
pubmed: 32727871
pii: gr.256933.119
doi: 10.1101/gr.256933.119
pmc: PMC7462079
doi:
Substances chimiques
RNA, Circular
0
RNA, Messenger
0
RNA-Binding Proteins
0
Inosine
5A614L51CT
ADAR1 protein, mouse
EC 3.5.4.4
ADAR2 protein, mouse
EC 3.5.4.4
Adenosine Deaminase
EC 3.5.4.4
Adenosine
K72T3FS567
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1107-1118Subventions
Organisme : Austrian Science Fund FWF
ID : P 30505
Pays : Austria
Informations de copyright
© 2020 Kapoor et al.; Published by Cold Spring Harbor Laboratory Press.
Références
Neuron. 2015 Jul 1;87(1):14-27
pubmed: 26139367
J Biol Chem. 2004 Feb 6;279(6):4894-902
pubmed: 14615479
Genome Biol. 2016 Nov 25;17(1):239
pubmed: 27887629
Nature. 2011 Jan 20;469(7330):343-9
pubmed: 21248841
Nature. 2000 Jul 6;406(6791):78-81
pubmed: 10894545
Methods Mol Biol. 2016;1402:229-241
pubmed: 26721495
Nature. 2017 Oct 11;550(7675):249-254
pubmed: 29022589
Curr Biol. 1997 Jul 1;7(7):R437-9
pubmed: 9210370
Bioessays. 2016 Jan;38(1):41-9
pubmed: 26612485
Nucleic Acids Res. 2019 Jan 10;47(1):3-14
pubmed: 30462291
Cell Rep. 2015 Jan 13;10(2):170-7
pubmed: 25558066
Nucleic Acids Res. 2014 Jan;42(Database issue):D109-13
pubmed: 24163250
Genome Res. 2018 Jun;28(6):812-823
pubmed: 29724793
Genome Res. 2019 Sep;29(9):1453-1463
pubmed: 31427386
J Comput Biol. 2004;11(2-3):377-94
pubmed: 15285897
J Biol Chem. 2004 Feb 6;279(6):4952-61
pubmed: 14613934
Nat Struct Mol Biol. 2013 Nov;20(11):1333-9
pubmed: 24077224
Nat Immunol. 2009 Jan;10(1):109-15
pubmed: 19060901
Nucleic Acids Res. 2016 Jul 27;44(13):6398-408
pubmed: 27112566
Bioinformatics. 2016 Apr 1;32(7):1094-6
pubmed: 26556385
RNA Biol. 2018;15(7):877-885
pubmed: 30064337
Genome Res. 2014 Nov;24(11):1774-86
pubmed: 25258385
Cell Rep. 2014 Nov 20;9(4):1482-94
pubmed: 25456137
Nucleic Acids Res. 2013 Jan;41(Database issue):D258-61
pubmed: 23074185
Chem Biol. 2010 Jul 30;17(7):675-6
pubmed: 20659677
Immunity. 2015 Nov 17;43(5):933-44
pubmed: 26588779
Cell. 1993 Dec 31;75(7):1361-70
pubmed: 8269514
Nat Rev Genet. 2018 Aug;19(8):473-490
pubmed: 29692414
EMBO J. 2011 Aug 16;30(20):4211-22
pubmed: 21847096
RNA Biol. 2015;12(12):1391-401
pubmed: 26512413
Nucleic Acids Res. 2020 Apr 6;48(6):3286-3303
pubmed: 31956894
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Nat Rev Mol Cell Biol. 2016 Feb;17(2):83-96
pubmed: 26648264
Mol Cell. 2015 Jun 4;58(5):870-85
pubmed: 25921068
RNA Biol. 2016;13(1):15-24
pubmed: 26669816
Nature. 2013 Mar 21;495(7441):333-8
pubmed: 23446348
RNA. 2013 May;19(5):591-604
pubmed: 23474544
Nucleic Acids Res. 2004 Apr 15;32(7):2113-22
pubmed: 15087490
Nucleic Acids Res. 2013 Jan;41(2):1113-23
pubmed: 23172291
BMC Genomics. 2016 Jan 11;17 Suppl 1:5
pubmed: 26817607
RNA. 2003 Mar;9(3):309-18
pubmed: 12592005
RNA. 2008 May;14(5):802-13
pubmed: 18369186
Nature. 1999 May 6;399(6731):75-80
pubmed: 10331393
Commun Biol. 2019 Jan 14;2:19
pubmed: 30652130
Genome Res. 2012 Oct;22(10):2008-17
pubmed: 22722343
BMC Bioinformatics. 2014 Dec 16;15:364
pubmed: 25511303
Nucleic Acids Res. 2007;35(11):3723-32
pubmed: 17517775
Science. 2015 Sep 4;349(6252):1115-20
pubmed: 26275108
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7
pubmed: 27141961
RNA Biol. 2013 Oct;10(10):1611-7
pubmed: 24025532
Elife. 2016 Feb 01;5:e11752
pubmed: 26829591
Nat Commun. 2011;2:319
pubmed: 21587236
Genome Biol. 2017 Sep 5;18(1):166
pubmed: 28874170
J Cell Biol. 2016 Apr 11;213(1):15-22
pubmed: 27044895
Proc Natl Acad Sci U S A. 1962 Apr 15;48:613-6
pubmed: 13865603
Methods Mol Biol. 2014;1126:83-96
pubmed: 24549657