TY - JOUR
T1 - Translation of CircRNAs
AU - Pamudurti, Nagarjuna Reddy
AU - Bartok, Osnat
AU - Jens, Marvin
AU - Ashwal-Fluss, Reut
AU - Stottmeister, Christin
AU - Ruhe, Larissa
AU - Hanan, Mor
AU - Wyler, Emanuel
AU - Perez-Hernandez, Daniel
AU - Ramberger, Evelyn
AU - Shenzis, Shlomo
AU - Samson, Moshe
AU - Dittmar, Gunnar
AU - Landthaler, Markus
AU - Chekulaeva, Marina
AU - Rajewsky, Nikolaus
AU - Kadener, Sebastian
N1 - Funding Information:
We thank M. Marr for reagents and Y. Arava for help. S.K. is funded by the ERC Consolidator Grant (ERC Grant 647989). M.C., N.R., and L.R. are supported by the Einstein Foundation grant ?Single molecule RNA network.? E.R. was supported by the Berlin School of Integrative Oncology (grant GSC 1091). M.J. received a fellowship from DFG (GRK 1772). C.S. is funded by BIF. N.R.P. is funded by a JBC fellowship.
Publisher Copyright:
© 2017 The Author(s)
PY - 2017/4/6
Y1 - 2017/4/6
N2 - 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.
AB - 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.
KW - cap-independent
KW - circRNA
KW - muscleblind
KW - translation
UR - https://www.scopus.com/pages/publications/85016009117
U2 - 10.1016/j.molcel.2017.02.021
DO - 10.1016/j.molcel.2017.02.021
M3 - Article
C2 - 28344080
AN - SCOPUS:85016009117
SN - 1097-2765
VL - 66
SP - 9-21.e7
JO - Molecular Cell
JF - Molecular Cell
IS - 1
ER -