Functional proteins in the cell are translated from the messenger RNA (mRNA) molecules, constituting less than 5% of the cellular transcriptome. The majority of the RNA molecules in the cell are noncoding RNAs, including rRNA, tRNA, snRNA, piRNA, lncRNA, microRNA, and poorly characterized circular RNAs (circRNAs). Recent studies established that circRNAs regulate gene expression by associating with RNA‐binding proteins and microRNAs. With the growing understanding of circRNA functions, a subset of circRNAs has been reported to translate into proteins. Interestingly, the presence of Open Reading Frames (ORFs), N6‐methyladenosine (m6A) modifications, and internal ribosomal entry sites (IRES) in the circRNA sequences indicate their coding potential through the cap‐independent translation initiation mechanism. The purpose of this review is to highlight the mechanism of circRNA translation and the importance of circRNA‐encoded proteins (circ‐proteins) in cellular physiology and pathology. Here, we discuss the computational and molecular methods currently utilized to systematically identify translatable circRNAs and the functional characterization of the circ‐proteins. We foresee that the ongoing and future studies on circRNA translation will uncover the hidden proteome and their therapeutic implications in human health.
Financed by the National Centre for Research and Development under grant No. SP/I/1/77065/10 by the strategic scientific research and experimental development program:
SYNAT - “Interdisciplinary System for Interactive Scientific and Scientific-Technical Information”.