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Overview of circRNAs

Circular RNAs (circRNAs) represent a class of non-coding RNAs with the 3' and 5' ends covalently linked. They are generally produced by alternative splicing of pre-mRNA, in which a downstream splice donor is joined to an upstream splice receptor in a process known as "backsplicing". Some studies have found that circRNAs are expressed in diverse eukaryotic organisms and are conservative across mammals. Most circRNAs consist of a single exon or multiple exons and have tissue-specific expression patterns. circRNAs were once considered to be "junk" except the testis-specific circRNA from the sex-determining region Y. In recent years, the advent of next-generation sequencing and circRNA-specific bioinformatics algorithms enables the discovery of thousands of circRNAs in eukaryotes and further prediction of circRNA function and underlying mechanisms. Many circRNAs are found to exert important biological functions by acting as microRNA (miRNA) sponges, by regulating protein function or by being translated themselves in a cap-independent manner. RNA-seq has revealed dysregulation of many circRNAs in various diseases such as neurological disorders and cancer, suggesting their engagement in disease development and progression and their potential as biomarkers.

Figure 1. circRNA splicing and isoform diversity (Barrett and Salzman 2016).

Characteristics of circRNAs

1. Most circRNAs are found in the cytoplasm and are highly conservative in sequence.
2. circRNAs are generally stable and the half lives are 48h, while mRNA has 10h half lives.
3. circRNAs may show differential expression patterns across cells.
4. circRNA are formed by alternative splicing of pre-mRNA and some can be translated.
5. circRNAs can function as miRNA sponges and affect transcription and translation.

References:

1. Barrett S P, Salzman J. Circular RNAs: analysis, expression and potential functions. Development, 2016, 143(11): 1838-1847.
2. Kristensen L S, Andersen M S, Stagsted L V W, et al. The biogenesis, biology and characterization of circular RNAs. Nature Reviews Genetics, 2019, 20(11): 675-691.
3. Bolha L, Ravnik-Glavač M, Glavač D. Circular RNAs: biogenesis, function, and a role as possible cancer biomarkers[J]. International journal of genomics, 2017, 2017.