Genome-Wide Identification of Human RNA Editing Sites by Parallel DNA Capturing and Sequencing

被引:420
作者
Li, Jin Billy [1 ]
Levanon, Erez Y. [1 ]
Yoon, Jung-Ki [1 ]
Aach, John [1 ]
Xie, Bin [2 ]
LeProust, Emily [3 ]
Zhang, Kun [1 ]
Gao, Yuan [2 ,4 ]
Church, George M. [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[2] Virginia Commonwealth Univ, Ctr Study Biol Complex, Richmond, VA 23284 USA
[3] Agilent Technol, Genom Solut Unit, Santa Clara, CA 95051 USA
[4] Virginia Commonwealth Univ, Dept Comp Sci, Richmond, VA 23284 USA
关键词
ADENOSINE DEAMINASES; HUMAN TRANSCRIPTOME; ENZYME ADAR2; MICE; DEFICIENT; LETHALITY; CHANNELS; TARGETS; BRAIN;
D O I
10.1126/science.1170995
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Adenosine-to-inosine (A-to-I) RNA editing leads to transcriptome diversity and is important for normal brain function. To date, only a handful of functional sites have been identified in mammals. We developed an unbiased assay to screen more than 36,000 computationally predicted nonrepetitive A-to-I sites using massively parallel target capture and DNA sequencing. A comprehensive set of several hundred human RNA editing sites was detected by comparing genomic DNA with RNAs from seven tissues of a single individual. Specificity of our profiling was supported by observations of enrichment with known features of targets of adenosine deaminases acting on RNA (ADAR) and validation by means of capillary sequencing. This efficient approach greatly expands the repertoire of RNA editing targets and can be applied to studies involving RNA editing-related human diseases.
引用
收藏
页码:1210 / 1213
页数:4
相关论文
共 25 条
[1]   Widespread A-to-I RNA editing of alu-containing mRNAs in the human transcriptome [J].
Athanasiadis, A ;
Rich, A ;
Maas, S .
PLOS BIOLOGY, 2004, 2 (12) :2144-2158
[2]   RNA editing by adenosine deaminases that act on RNA [J].
Bass, BL .
ANNUAL REVIEW OF BIOCHEMISTRY, 2002, 71 :817-846
[3]   A survey of RNA editing in human brain [J].
Blow, M ;
Futreal, PA ;
Wooster, R ;
Stratton, MR .
GENOME RESEARCH, 2004, 14 (12) :2379-2387
[4]   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
[5]   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
[6]   A bioinformatic screen for novel A-I RNA editing sites reveals recoding editing in BC10 [J].
Clutterbuck, DR ;
Leroy, A ;
O'Connell, MA ;
Semple, CAM .
BIOINFORMATICS, 2005, 21 (11) :2590-2595
[7]   Is abundant A-to-I RNA editing primate-specific? [J].
Eisenberg, E ;
Nemzer, S ;
Kinar, Y ;
Sorek, R ;
Rechavi, G ;
Levanon, EY .
TRENDS IN GENETICS, 2005, 21 (02) :77-81
[8]   Screening of human SNP database identifies recoding sites of A-to-I RNA editing [J].
Gommans, Willemijn M. ;
Tatalias, Nicholas E. ;
Sie, Christina P. ;
Dupuis, Dylan ;
Vendetti, Nicholas ;
Smith, Lauren ;
Kaushal, Rikhi ;
Maas, Stefan .
RNA, 2008, 14 (10) :2074-2085
[9]   Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2 [J].
Higuchi, M ;
Stefan, M ;
Single, FN ;
Hartner, J ;
Rozov, A ;
Burnashev, N ;
Feldmeyer, D ;
Sprengel, R ;
Seeburg, PH .
NATURE, 2000, 406 (6791) :78-81
[10]   Nervous system targets of RNA editing identified by comparative genomics [J].
Hoopengardner, B ;
Bhalla, T ;
Staber, C ;
Reenan, R .
SCIENCE, 2003, 301 (5634) :832-836