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Mol Cell. 2017 Apr 6;66(1):9-21.e7. doi: 10.1016/j.molcel.2017.02.021. Epub 2017 Mar 23.

Translation of CircRNAs.

Author information

1
Biological Chemistry Department, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
2
Systems Biology of Gene Regulatory Elements, Max-Delbrück-Center for Molecular Medicine, Berlin 13125, Germany.
3
Non Coding RNAs and Mechanisms of Cytoplasmic Gene Regulation, Max-Delbrück-Center for Molecular Medicine, Berlin 13125, Germany.
4
RNA Biology and Posttranscriptional Regulation, Max-Delbrück-Center for Molecular Medicine, Berlin 13125, Germany.
5
Mass Spectrometry Core Unit, Max-Delbrück-Center for Molecular Medicine, Berlin 13125, Germany.
6
Biological Chemistry Department, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. Electronic address: skadener@mail.huji.ac.il.

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.

KEYWORDS:

cap-independent; circRNA; muscleblind; translation

Comment in

PMID:
28344080
PMCID:
PMC5387669
DOI:
10.1016/j.molcel.2017.02.021
[Indexed for MEDLINE]
Free PMC Article

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