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2017 ; 66
(1
): 9-21.e7
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Translation of CircRNAs
#MMPMID28344080
Pamudurti NR
; Bartok O
; Jens M
; Ashwal-Fluss R
; Stottmeister C
; Ruhe L
; Hanan M
; Wyler E
; Perez-Hernandez D
; Ramberger E
; Shenzis S
; Samson M
; Dittmar G
; Landthaler M
; Chekulaeva M
; Rajewsky N
; Kadener S
Mol Cell
2017[Apr]; 66
(1
): 9-21.e7
PMID28344080
show ga
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.
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