Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed

被引:1946
作者
Rybak-Wolf, Agnieszka [1 ]
Stottmeister, Christin [1 ]
Glazar, Petar [1 ]
Jens, Marvin [1 ]
Pino, Natalia [4 ]
Giusti, Sebastian [4 ]
Hanan, Mor [2 ]
Behm, Mikaela [3 ]
Bartok, Osnat [2 ]
Ashwal-Fluss, Reut [2 ]
Herzog, Margareta [1 ]
Schreyer, Luisa [1 ]
Papavasileiou, Panagiotis [1 ]
Ivanov, Andranik [1 ]
Ohman, Marie [3 ]
Refojo, Damian [4 ,5 ]
Kadener, Sebastian [2 ]
Rajewsky, Nikolaus [1 ]
机构
[1] Max Delbruck Ctr Mol Med, Syst Biol Gene Regulatory Elements, D-13125 Berlin, Germany
[2] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, IL-91904 Jerusalem, Israel
[3] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden
[4] Max Planck Inst Psychiat, Mol Neurobiol, D-80804 Munich, Germany
[5] Max Planck Gesell, CONICET Partner Inst, Inst Invest Biomed Buenos Aires IBioBA, Buenos Aires, DF, Argentina
基金
欧洲研究理事会; 以色列科学基金会;
关键词
EMBRYONAL CARCINOMA-CELLS; MESSENGER-RNA; EXON CIRCULARIZATION; MOUSE TESTIS; DROSOPHILA; ELEMENTS; GENOME; BIOGENESIS; REVEALS; REPEATS;
D O I
10.1016/j.molcel.2015.03.027
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
Circular RNAs (circRNAs) are an endogenous class of animal RNAs. Despite their abundance, their function and expression in the nervous system are unknown. Therefore, we sequenced RNA from different brain regions, primary neurons, isolated synapses, as well as during neuronal differentiation. Using these and other available data, we discovered and analyzed thousands of neuronal human and mouse circRNAs. circRNAs were extraordinarily enriched in the mammalian brain, well conserved in sequence, often expressed as circRNAs in both human and mouse, and sometimes even detected in Drosophila brains. circRNAs were overall upregulated during neuronal differentiation, highly enriched in synapses, and often differentially expressed compared to their mRNA isoforms. circRNA expression correlated negatively with expression of the RNA-editing enzyme ADAR1. Knockdown of ADAR1 induced elevated circRNA expression. Together, we provide a circRNA brain expression atlas and evidence for important circRNA functions and values as biomarkers.
引用
收藏
页码:870 / 885
页数:16
相关论文
共 36 条
[1]   circRNA Biogenesis Competes with Pre-mRNA Splicing [J].
Ashwal-Fluss, Reut ;
Meyer, Markus ;
Pamudurti, Nagarjuna Reddy ;
Ivanov, Andranik ;
Bartok, Osnat ;
Hanan, Mor ;
Evantal, Naveh ;
Memczak, Sebastian ;
Rajewsky, Nikolaus ;
Kadener, Sebastian .
MOLECULAR CELL, 2014, 56 (01) :55-66
[2]   Dendritic mRNA: transport, translation and function [J].
Bramham, Clive R. ;
Wells, David G. .
NATURE REVIEWS NEUROSCIENCE, 2007, 8 (10) :776-789
[3]   Subdivision of large introns in Drosophila by recursive splicing at nonexonic elements [J].
Burnette, JM ;
Miyamoto-Sato, E ;
Schaub, MA ;
Conklin, J ;
Lopez, AJ .
GENETICS, 2005, 170 (02) :661-674
[4]   CIRCULAR TRANSCRIPTS OF THE TESTIS-DETERMINING GENE SRY IN ADULT-MOUSE TESTIS [J].
CAPEL, B ;
SWAIN, A ;
NICOLIS, S ;
HACKER, A ;
WALTER, M ;
KOOPMAN, P ;
GOODFELLOW, P ;
LOVELLBADGE, R .
CELL, 1993, 73 (05) :1019-1030
[5]   Ensembl 2015 [J].
Cunningham, Fiona ;
Amode, M. Ridwan ;
Barrell, Daniel ;
Beal, Kathryn ;
Billis, Konstantinos ;
Brent, Simon ;
Carvalho-Silva, Denise ;
Clapham, Peter ;
Coates, Guy ;
Fitzgerald, Stephen ;
Gil, Laurent ;
Giron, Carlos Garcia ;
Gordon, Leo ;
Hourlier, Thibaut ;
Hunt, Sarah E. ;
Janacek, Sophie H. ;
Johnson, Nathan ;
Juettemann, Thomas ;
Kaehaeri, Andreas K. ;
Keenan, Stephen ;
Martin, Fergal J. ;
Maurel, Thomas ;
McLaren, William ;
Murphy, Daniel N. ;
Nag, Rishi ;
Overduin, Bert ;
Parker, Anne ;
Patricio, Mateus ;
Perry, Emily ;
Pignatelli, Miguel ;
Riat, Harpreet Singh ;
Sheppard, Daniel ;
Taylor, Kieron ;
Thormann, Anja ;
Vullo, Alessandro ;
Wilder, Steven P. ;
Zadissa, Amonida ;
Aken, Bronwen L. ;
Birney, Ewan ;
Harrow, Jennifer ;
Kinsella, Rhoda ;
Muffato, Matthieu ;
Ruffier, Magali ;
Searle, Stephen M. J. ;
Spudich, Giulietta ;
Trevanion, Stephen J. ;
Yates, Andy ;
Zerbino, Daniel R. ;
Flicek, Paul .
NUCLEIC ACIDS RESEARCH, 2015, 43 (D1) :D662-D669
[6]   Alu elements shape the primate transcriptome by cis-regulation of RNA editing [J].
Daniel, Chammiran ;
Silberberg, Gilad ;
Behm, Mikaela ;
Ohman, Marie .
GENOME BIOLOGY, 2014, 15 (02)
[7]   Inverted repeats are necessary for circularization of the mouse testis Sry transcript [J].
Dubin, RA ;
Kazmi, MA ;
Ostrer, H .
GENE, 1995, 167 (1-2) :245-248
[8]   An integrated encyclopedia of DNA elements in the human genome [J].
Dunham, Ian ;
Kundaje, Anshul ;
Aldred, Shelley F. ;
Collins, Patrick J. ;
Davis, CarrieA. ;
Doyle, Francis ;
Epstein, Charles B. ;
Frietze, Seth ;
Harrow, Jennifer ;
Kaul, Rajinder ;
Khatun, Jainab ;
Lajoie, Bryan R. ;
Landt, Stephen G. ;
Lee, Bum-Kyu ;
Pauli, Florencia ;
Rosenbloom, Kate R. ;
Sabo, Peter ;
Safi, Alexias ;
Sanyal, Amartya ;
Shoresh, Noam ;
Simon, Jeremy M. ;
Song, Lingyun ;
Trinklein, Nathan D. ;
Altshuler, Robert C. ;
Birney, Ewan ;
Brown, James B. ;
Cheng, Chao ;
Djebali, Sarah ;
Dong, Xianjun ;
Dunham, Ian ;
Ernst, Jason ;
Furey, Terrence S. ;
Gerstein, Mark ;
Giardine, Belinda ;
Greven, Melissa ;
Hardison, Ross C. ;
Harris, Robert S. ;
Herrero, Javier ;
Hoffman, Michael M. ;
Iyer, Sowmya ;
Kellis, Manolis ;
Khatun, Jainab ;
Kheradpour, Pouya ;
Kundaje, Anshul ;
Lassmann, Timo ;
Li, Qunhua ;
Lin, Xinying ;
Marinov, Georgi K. ;
Merkel, Angelika ;
Mortazavi, Ali .
NATURE, 2012, 489 (7414) :57-74
[9]  
GRAY EG, 1960, J PHYSIOL-LONDON, V153, pP35
[10]   Natural RNA circles function as efficient microRNA sponges [J].
Hansen, Thomas B. ;
Jensen, Trine I. ;
Clausen, Bettina H. ;
Bramsen, Jesper B. ;
Finsen, Bente ;
Damgaard, Christian K. ;
Kjems, Jorgen .
NATURE, 2013, 495 (7441) :384-388