circRNA Biogenesis Competes with Pre-mRNA Splicing

被引：4064

作者：

Ashwal-Fluss, Reut ^{[1
]}

Meyer, Markus ^{[2
]}

Pamudurti, Nagarjuna Reddy ^{[1
]}

Ivanov, Andranik ^{[2
]}

Bartok, Osnat ^{[1
]}

Hanan, Mor ^{[1
]}

Evantal, Naveh ^{[1
]}

Memczak, Sebastian ^{[2
]}

Rajewsky, Nikolaus ^{[2
]}

Kadener, Sebastian ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Dept Biol Chem, Silberman Inst Life Sci, IL-91904 Jerusalem, Israel

[2] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany

来源：

MOLECULAR CELL | 2014年 / 56卷 / 01期

基金：

欧洲研究理事会;

关键词：

CIRCULAR RNAS; MOUSE TESTIS; DROSOPHILA; GENE; EXON; TRANSCRIPTION; REPEATS; SRY;

D O I：

10.1016/j.molcel.2014.08.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Circular RNAs (circRNAs) are widely expressed noncoding RNAs. However, their biogenesis and possible functions are poorly understood. Here, by studying circRNAs that we identified in neuronal tissues, we provide evidence that animal circRNAs are generated cotranscriptionally and that their production rate is mainly determined by intronic sequences. We demonstrate that circularization and splicing compete against each other. These mechanisms are tissue specific and conserved in animals. Interestingly, we observed that the second exon of the splicing factor muscleblind (MBL/MBNL1) is circularized in flies and humans. This circRNA (circMbl) and its flanking introns contain conserved muscleblind binding sites, which are strongly and specifically bound by MBL. Modulation of MBL levels strongly affects circMbl biosynthesis, and this effect is dependent on the MBL binding sites. Together, our data suggest that circRNAs can function in gene regulation by competing with linear splicing. Furthermore, we identified muscleblind as a factor involved in circRNA biogenesis.

引用

页码：55 / 66

页数：12

共 33 条

[1]

Coupling mRNA processing with transcription in time and space [J].

Bentley, David L. .

NATURE REVIEWS GENETICS, 2014, 15 (03) :163-175

[2]

Inverse splicing of a discontinuous pre-mRNA intron generates a circular exon in a HeLa cell nuclear extract [J].

Braun, S ;

Domdey, H ;

Wiebauer, K .

NUCLEIC ACIDS RESEARCH, 1996, 24 (21) :4152-4157

[3]

CHARACTERIZATION AND USE OF THE DROSOPHILA METALLOTHIONEIN PROMOTER IN CULTURED DROSOPHILA-MELANOGASTER CELLS [J].

BUNCH, TA ;

GRINBLAT, Y ;

GOLDSTEIN, LSB .

NUCLEIC ACIDS RESEARCH, 1988, 16 (03) :1043-1061

[4]

TDP-43: new aspects of autoregulation mechanisms in RNA binding proteins and their connection with human disease [J].

Buratti, Emanuele ;

Baralle, Francisco E. .

FEBS JOURNAL, 2011, 278 (19) :3530-3538

[5]

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

[6]

COULTER DE, 1985, J BIOL CHEM, V260, P3190

[7]

Transcriptome-wide discovery of circular RNAs in Archaea [J].

Danan, Miri ;

Schwartz, Schraga ;

Edelheit, Sarit ;

Sorek, Rotem .

NUCLEIC ACIDS RESEARCH, 2012, 40 (07) :3131-3142

[8]

A slow RNA polymerase II affects alternative splicing in vivo [J].

de la Mata, M ;

Alonso, CR ;

Kadener, S ;

Fededa, JP ;

Blaustein, M ;

Pelisch, F ;

Cramer, P ;

Bentley, D ;

Kornblihtt, AR .

MOLECULAR CELL, 2003, 12 (02) :525-532

[9]

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

[10]

The Xist lncRNA Exploits Three-Dimensional Genome Architecture to Spread Across the X Chromosome [J].

Engreitz, Jesse M. ;

Pandya-Jones, Amy ;

McDonel, Patrick ;

Shishkin, Alexander ;

Sirokman, Klara ;

Surka, Christine ;

Kadri, Sabah ;

Xing, Jeffrey ;

Goren, Alon ;

Lander, Eric S. ;

Plath, Kathrin ;

Guttman, Mitchell .

SCIENCE, 2013, 341 (6147) :767-+

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