Adenosine deaminases that act on RNA induce reproducible changes in abundance and sequence of embryonic miRNAs

被引:65
作者
Vesely, Cornelia [1 ]
Tauber, Stefanie [2 ,3 ]
Sedlazeck, Fritz J. [2 ,3 ]
von Haeseler, Arndt [2 ,3 ]
Jantsch, Michael F. [1 ]
机构
[1] Univ Vienna, Dept Chromosome Biol, Max F Perutz Labs, A-1030 Vienna, Austria
[2] Med Univ Vienna, Univ Vienna, Max F Perutz Labs, Ctr Integrat Bioinformat Vienna, A-1030 Vienna, Austria
[3] Univ Vet Med, A-1030 Vienna, Austria
基金
奥地利科学基金会;
关键词
EDITING SITES; ADAR; IDENTIFICATION; TARGETS; EXPRESSION; DEFICIENT; LETHALITY; MUTATION; BINDING;
D O I
10.1101/gr.133025.111
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Adenosine deaminases that act on RNA bind double-stranded and structured RNAs and convert adenosines to inosines by hydrolytic deamination. Inosines are recognized as guanosines, and, hence, RNA editing alters the sequence information but also structure of RNAs. Editing by ADARs is widespread and essential for normal life and development. Precursors of miRNAs are abundantly edited by ADARs, but neither the abundance nor the consequences of miRNA editing has been firmly established. Using transgenic mouse embryos that are deficient in the two enzymatically active editing enzymes ADAR and ADARB1, we compare relative frequencies but also sequence composition of miRNAs in these genetically modified backgrounds to wild-type mice by "next-generation sequencing." Deficiency of ADARB1 leads to a reproducible change in abundance of specific miRNAs and their predicted targets. Changes in miRNA abundance seem unrelated to editing events. Additional deletion of ADAR has surprisingly little impact on the mature miRNA repertoire, indicating that miRNA expression is primarily dependent on ADARB1. A-to-G transitions reflecting A-to-I editing events can be detected at few sites and at low frequency during the early embryonic stage investigated. Again, most editing events are ADARB1-dependent with only few editing sites being specifically edited by ADAR. Besides known editing events in miRNAs, a few novel, previously unknown editing events were identified. Some editing events are located to the seed region of miRNAs, opening the possibility that editing leads to their retargeting.
引用
收藏
页码:1468 / 1476
页数:9
相关论文
共 42 条
[1]  
[Anonymous], 2011, EMBNET J
[2]   ADAR Proteins: Double-stranded RNA and Z-DNA Binding Domains [J].
Barraud, Pierre ;
Allain, Frederic H. -T. .
ADENOSINE DEAMINASES ACTING ON RNA (ADARS) AND A-TO-I EDITING, 2012, 353 :35-60
[3]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[5]   RNA editing of human microRNAs [J].
Blow, Matthew J. ;
Grocock, Russell J. ;
van Dongen, Stijn ;
Enright, Anton J. ;
Dicks, Ed ;
Futreal, P. Andrew ;
Wooster, Richard ;
Stratton, Michael R. .
GENOME BIOLOGY, 2006, 7 (04)
[6]   Glutamatergic neurotransmission in the synapsin I and II double knock-out mouse [J].
Bogen, Inger Lise ;
Jensen, Vidar ;
Hvalby, Oivind ;
Walaas, S. Ivar .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2011, 22 (04) :400-407
[7]   EARLY-ONSET EPILEPSY AND POSTNATAL LETHALITY ASSOCIATED WITH AN EDITING-DEFICIENT GLUR-B ALLELE IN MICE [J].
BRUSA, R ;
ZIMMERMANN, F ;
KOH, DS ;
FELDMEYER, D ;
GASS, P ;
SEEBURG, PH ;
SPRENGEL, R .
SCIENCE, 1995, 270 (5242) :1677-1680
[8]   Regulation of serotonin-2C receptor G-protein coupling by RNA editing [J].
Burns, CM ;
Chu, H ;
Rueter, SM ;
Hutchinson, LK ;
Canton, H ;
SandersBush, E ;
Emeson, RB .
NATURE, 1997, 387 (6630) :303-308
[9]   Mammalian microRNAs: experimental evaluation of novel and previously annotated genes [J].
Chiang, H. Rosaria ;
Schoenfeld, Lori W. ;
Ruby, J. Graham ;
Auyeung, Vincent C. ;
Spies, Noah ;
Baek, Daehyun ;
Johnston, Wendy K. ;
Russ, Carsten ;
Luo, Shujun ;
Babiarz, Joshua E. ;
Blelloch, Robert ;
Schroth, Gary P. ;
Nusbaum, Chad ;
Bartel, David P. .
GENES & DEVELOPMENT, 2010, 24 (10) :992-1009
[10]   Predicting sites of ADAR editing in double-stranded RNA [J].
Eggington, Julie M. ;
Greene, Tom ;
Bass, Brenda L. .
NATURE COMMUNICATIONS, 2011, 2