Translation of Circular RNAs: Functions of Translated Products and Related Bioinformatics Approaches

Over the past two decades, studies have discovered a special form of alternative splicing (AS) that produces a circular form of RNA. This stands in contrast to normal AS, which produces a linear form of RNA. Although these circRNAs have garnered considerable attention in the scientific community for their biogenesis and functions, the focus of these studies has been on the regulatory role of circRNAs with the assumption that circRNAs are non-coding. As non-coding RNAs, they may regulate mRNA transcription, tumor initiation, and translation by sponging miRNAs and RNA-binding proteins (RBPs). In addition to these regulatory roles of circRNAs, however, recent studies have provided strong evidence for their translation. The translation of circRNAs is expected to have an important role in promoting cancer cell growth and activating molecular pathways related to cancer development. In some cases, the translation of circRNAs is shown to be efficiently driven by an internal ribosome entry site (IRES). The development of a computational tool for identifying and characterizing the translation of circRNAs using high-throughput sequencing and IRES increases identifiable proteins translated from circRNAs. In turn, it has a substantial impact on helping researchers understand the functional role of proteins derived from circRNAs. New web resources for aggregating, cataloging, and visualizing translational information of circRNAs derived from previous studies have been developed. In this paper, general concepts of circRNA, circRNA biogenesis, translation of circRNA, and existing circRNA tools and databases are summarized to provide new insight into circRNA studies.