How much do you know about circRNA research? – II

The discovery of the novel protein-encoding function of circRNA and its role in clinical sciences.

The circRNA field is relatively new – in the previous blog (https://www.rna-seqblog.com/how-much-do-you-know-about-circrna-research/), we got acquainted with the basic roles of circRNA, particularly with its main function as a so-called molecular sponge. This class of RNAs is very abundant, with tissue-specific patterns. The circRNA also serves during transcription regulation and mRNA precursor splicing competition. As we dive deeper into circRNA biology, we find more exciting functions of circRNA, specifically its translation potential. We will review two specific roles of circRNAs in encoding proteins.

Silencing role in gene expression

There is a potential new function of circRNAs revealed recently. While it has been known that circRNAs express gene expression by acting as miRNA sponges, the authors’ hypothesis was that circRNA also encode small peptides. These small peptides may have a role in tumor pathogenesis. Zheng et al. focused on colon cancer: they found the particular up-regulated circRNA and to identify its function, the authors did the studies, in which they silenced the specific circRNA and explored its protein-coding ability ^[1]. Interestingly, the circRNA silencing suppressed the proliferation of colon cancer cells. Moreover, the start codon mutation of the circRNA impairs its protein-coding function.

Encoding protein in signaling pathways

The circRNA can have potentially crucial roles in a multitude of biological processes, including signaling. For example, Wu et al suggested that circRNA encodes a protein, involved in the Hedgehog pathway in glioblastoma. The study identified a novel protein SMO-193a.a. and after studying the function of this protein, it became evident that it is required for SMO activation via sonic hedgehog (Shh) ^[2].

The above shows novel functions of circRNA. Next-generation sequencing (NGS), performs as a common research approach, facilitates to the investigation of circRNA molecules. With combination of translation group, functional verification and mechanism research, circRNA sequencing (circRNA-seq) unveils the translation potential of circRNA. #Novogene provides circRNA-seq and omics sequencing analysis services to a wide range of samples. Find more services on Novogene’s website (en.novogene.com) or contact us here.

 

References

[1] Zheng X, Chen L, Zhou Y, et al. A novel protein encoded by a circular RNA circPPP1R12A promotes tumor pathogenesis and metastasis of colon cancer via Hippo-YAP signaling [J]. Molecular Cancer, 2019, 18:47.

[2] Wu X, Xiao S, Zhang M, et al. A novel protein encoded by circular SMO RNA is essential for Hedgehog signaling activation and glioblastoma tumorigenicity [J]. Genome Biology, 2021, 22:33.