Translatable circRNAs and lncRNAs: Driving mechanisms and functions of their translation products

Long non-coding RNA (lncRNAs) are functional RNA segments longer than 200 nucleotides, which are considered a redundant transcriptional product. Recently, lncRNAs have been shown to harbor open reading frame (ORF) sequences and encode proteins/peptides. Circular RNAs (circRNAs) have long been considered as another type of non-coding RNA (ncRNA) due to the absence of the 5' cap structure. However, recent studies have shown that they also have ORFs in their sequences. CircRNAs can be translated into proteins via internal ribosome entry site (IRES)-driven or N6-methyladenosine (m6A)-mediated initiation. To date, several translatable circRNAs and lncRNAs have been identified in Drosophila, mice, and human myoblasts, as well as in different cancers, such as glioma, hepatocellular carcinoma, and colon cancer. In this article, we review the mechanisms that drive translation of circRNAs and lncRNAs. Moreover, we discuss the research methods and tools available to identify their translation products and validate the function of these bioactive proteins/peptides in physiology and cancer.