Ricerc@Sapienza

Circular RNAs (circRNAs) are RNA species formed via a non-canonical splicing event, called back-splicing, through which a downstream 5' splice site interacts with an upstream 3' splice site forming a covalent bond, leading to the formation of a circular molecule.
The rate of discovery of new circRNAs in different cellular systems is not paralleled by an adequate characterization of their function. Important clues about the functionality of an RNA molecule may be deduced from the knowledge of its secondary structure. Although bioinformatic tools are available to predict the secondary structure of circular RNA molecules, no one has ever used them on a large scale to study global and local properties of circRNAs secondary structure. In the first part of the proposed project, a large set of human and murine circRNAs originated from pre-mRNAs will be folded in silico in order to assess whether they have a particularly high or low secondary structure content. Indicatively, a low level of secondary structure could suggest a protein-coding activity, while structured RNAs are more likely to exert their function directly, without being translated. Since we do not expect all circRNAs to play the same role, we will evaluate whether differences in secondary structure content correlate with differences in the mRNA region from which they originate.
CircRNAs will also be scanned in search for common sequence and structure motifs. Special attention will be paid to patterns found in the region around the back-splicing junction site, whose sequence represents the distinctive feature of circRNAs. The involvement of the identified motifs in mediating the interaction of circRNAs with proteins will be investigated by searching for their presence in binding sites found in publicly available CLIP-Seq data.
As a final step, we will write an algorithm for the prediction of circRNA-protein interactions exploiting the inferred secondary structure of circRNAs.