The Roles of CircRNAs in Mitochondria

Abstract

Mitochondria participate in varieties of cellular events. It is widely accepted that human mitochondrial genome encodes 13 proteins, 2 rRNAs, and 22 tRNAs. Gene variation derived from human nuclear genome cannot completely explain mitochondrial diseases. The advent of high-throughput sequencing coupled with novel bioinformatic analyses decode the complexity of mitochondria-derived transcripts. Recently, circular RNAs (circRNAs) from both human mitochondrial genome and nuclear genome have been found to be located at mitochondria. Studies about the roles and molecular mechanisms underlying trafficking of the nucleus encoded circRNAs to mitochondria and mitochondria encoded circRNAs to the nucleus or cytoplasm in mammals are only beginning to emerge. These circRNAs have been associated with a variety of diseases, especially cancers. Here, we discuss the emerging field of mitochondria-located circRNAs by reviewing their identification, expression patterns, regulatory roles, and functional mechanisms. Mitochondria-located circRNAs have regulatory roles in cellular physiology and pathology. We also highlight future perspectives and challenges in studying mitochondria-located circRNAs, as well as their potential biomedical applications.

Keywords: circular RNAs; mitochondria; mitochondrial genome; noncoding RNAs; nuclear genome.

Figure 1

Human mitochondrial DNA composition. Heavy strand in red and light strand in blue. The rRNAs, mRNAs, and tRNAs were separately labeled in black, white, and purple. HSP and LSP are the promoters of heavy and light strands seperately. The validated mecciRNAs were marked in black. The figure was generated by using BioRender (https://app.biorender.com/).

Figure 2

Mitochondria-located circRNAs derived from nuclear and mitochondrial genome. The figure was generated by using BioRender (https://app.biorender.com/).