RT Journal Article SR Electronic T1 Noncoding AUG circRNAs constitute an abundant and conserved subclass of circles JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201900398 DO 10.26508/lsa.201900398 VO 2 IS 3 A1 Lotte VW Stagsted A1 Katrine M Nielsen A1 Iben Daugaard A1 Thomas B Hansen YR 2019 UL https://www.life-science-alliance.org/content/2/3/e201900398.abstract AB Circular RNAs (circRNAs) are a subset of noncoding RNAs previously considered as products of missplicing. Now, circRNAs are considered functional molecules, although to date, only few functions have been experimentally validated. Here, based on RNA sequencing from the ENCODE consortium, we identify and characterize a subset of circRNAs, coined AUG circRNAs, encompassing the annotated translational start codon from the protein-coding host genes. AUG circRNAs are more abundantly expressed and conserved than other groups of circRNAs, and they display flanking sequences that suggest an Alu-independent mechanism of biogenesis. The AUG circRNAs contain part of bona fide open reading frame, and in the recent years, several studies have reported cases of circRNA translation. However, using thorough cross-species analysis, extensive ribosome profiling, proteomics analyses, and experimental data on a selected panel of AUG circRNAs, we observe no indications of translation of AUG circRNAs or any other circRNAs. Our data provide a comprehensive classification of circRNAs and, collectively, the data suggest that the AUG circRNAs constitute an abundant subclass of circRNAs produced independently of primate-specific Alu elements.