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

AGNIESZKA RYBAK-WOLF; CHRISTIN STOTTMEISTER; PETAR GLAZAR; MARVIN JENS; NATALIA S. PINO; SEBASTIAN A. GIUSTI; MOR HANAN; MIKAELA BEHM; OSNAT BARTOK; REUT ASHWAL-FLUSS; MARGARETA HERZOG; LUISA SCHREYER; PANAGIOTIS PAPAVASILEIOU; ANDRANIK IVANOV; MARIE OEHMAN; DAMIAN REFOJO; SEBASTIAN KADENER; NIKOLAUS RAJEWSKY

MOLECULAR CELL

CELL PRESS

Lugar: United States; Año: 2015 p. 870 - 885

1097-2765

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.