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Translation of CircRNAs.

Molecular cell (2017-03-28)
Nagarjuna Reddy Pamudurti, Osnat Bartok, Marvin Jens, Reut Ashwal-Fluss, Christin Stottmeister, Larissa Ruhe, Mor Hanan, Emanuel Wyler, Daniel Perez-Hernandez, Evelyn Ramberger, Shlomo Shenzis, Moshe Samson, Gunnar Dittmar, Markus Landthaler, Marina Chekulaeva, Nikolaus Rajewsky, Sebastian Kadener
ABSTRACT

Circular RNAs (circRNAs) are abundant and evolutionarily conserved RNAs of largely unknown function. Here, we show that a subset of circRNAs is translated in vivo. By performing ribosome footprinting from fly heads, we demonstrate that a group of circRNAs is associated with translating ribosomes. Many of these ribo-circRNAs use the start codon of the hosting mRNA, are bound by membrane-associated ribosomes, and have evolutionarily conserved termination codons. In addition, we found that a circRNA generated from the muscleblind locus encodes a protein, which we detected in fly head extracts by mass spectrometry. Next, by performing in vivo and in vitro translation assays, we show that UTRs of ribo-circRNAs (cUTRs) allow cap-independent translation. Moreover, we found that starvation and FOXO likely regulate the translation of a circMbl isoform. Altogether, our study provides strong evidence for translation of circRNAs, revealing the existence of an unexplored layer of gene activity.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-V5 antibody, Mouse monoclonal, clone V5-10, purified from hybridoma cell culture
Sigma-Aldrich
Anti-α-Tubulin antibody, Mouse monoclonal, clone DM1A, purified from hybridoma cell culture