The emerging roles of exosomal circRNAs in diseases

Exosomes, the nanoscale phospholipid bilayer vesicles, enriched in selected proteins, nucleic acids and lipids, which they participated in a variety of biological processes in the body, including physiology and pathology. CircRNAs (circular RNAs) are a class of single-stranded closed molecules with tissue development specific expression patterns that have crucial regulatory functions in various diseases. Non-coding RNAs (such as microRNAs and long non‑coding RNAs) in exosomes have also been shown to play an important regulatory role in humans. However, little research has focused on exosomal circRNAs. Recently, CircRNAs have been identified to be enriched and stably expressed in exosomes. Researchers from the South China University of Technology summarize the biogenesis and biological functions of exosomes and circRNA, and further revealed the potential role of exosome-derived circRNA in different diseases. They propose its use as a diagnostic marker and therapeutic punctuation for diseases, especially in cancer.

Biogenesis and function of circRNAs

Fig. 2

a Intron pairing driven circularization. The cycle driven by intron pairing is realized by direct base pairing of introns on both sides of complementary sequences or reverse repeats. The introns are removed or retained to form ecircRNA or EIciRNA. b RBP pairing driven circularization. The RBPs are embedded into the precursor RNA during transcription and bind to the lateral intron sequence, causing the precursor RNA to bend and fold to form a circular cross region. c Lariat-driven circularization. It takes place in exon jump events or the removal of introns from the precursor mRNAs. d TricRNAs are synthesized from introns spliced from pre-tRNA. The tRNA splicing endonuclease complex cuts an intron-containing pre-tRNA at a canonical bulge-helix bulge (BHB) motif; and the intron termini are also joined by RtcB ligase to form a stable circRNA, named tricRNA. e EIciRNAs or ciRNAs can interact with transcription complexes in the promoter region of their host gene to induce gene transcription by interacting with U1 snRNP or RNA pol II. f The back-splicing and linear splicing can compete with each other during splicing. As a result, a linear RNA or an ecircRNA is generated. g circRNAs can act as miRNA sponges to inhibit miRNA activity. h circRNAs can interact with RBPs and affect their functions and translocations. i circRNAs have protein-coding capacity and can encode proteins

Guo X, Tan W, Wang, C. (2020) The emerging roles of exosomal circRNAs in diseases. Clin Transl Oncol [online ahead of print]. [article]

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