Regulation of Transcription by Circular RNAs

Circular RNAs (circRNAs) are a class of noncoding RNA that are present in wide variety of cells in various tissue types across species. They are non-polyadenylated, single-stranded, covalently closed RNAs. CircRNAs are more stable than other RNAs due to lack of 5' or 3' end leading to resistance to exonuclease digestion. The length of circRNAs varies from 1 to 5 exons with retention of introns in mature circRNAs with ~25% frequency. They are primarily found in the cytosol within the cell although the mechanism of their nuclear export remains elusive. However, there is a subpopulation of circRNAs that remain in the nucleus and regulate RNA-Pol-II-mediated transcription. Bioinformatic approaches mining RNA sequencing data enabled genome-wide identification of circRNAs. In mammalian genome over 20% of the expressed genes in cells and tissues can produce these transcripts. Owing to their abundance, stability, and diverse expression profile, circRNAs likely play a pivotal role in regulatory pathways controlling lineage determination, cell differentiation, and function of various cell types. Yet, the impact of circRNA-mediated regulation on various cell transcriptome remains largely unknown. In this chapter, we will review the regulatory effects of circRNAs in the transcription of their own or other genes. Also, we will discuss the association of circRNAs with miRNAs and RNA-binding proteins (RBPs), with special reference to Drosophila circMbl and their role as an "mRNA trap," which might play a role in its regulatory potential transcriptionally or posttranscriptionally.