How much do you know about circRNA research?

circRNAs: uncovering the functions of novel non-coding sequences – from developmental biology to anti-cancer therapies

Summary

What is circRNA? (Research on the function of circRNA; research hotspots in life sciences and medicine)

Circular RNAs (circRNAs) are a new class of regulatory non-coding RNAs with a covalently closed structure of the ribose phosphate backbone. Circular RNAs are present in eukaryotes and their expression patterns are tissue- or cell-specific, as well as they tend to accumulate in specific cell types while being very stable ^[2]. Most of them are expressed from protein-coding genes and come from canonical splice sites. Circular RNAs contain single or multiple exons and lack poly(A) and cap and are resistant to exonuclease degradation due to circRNA specific structure.

The most popular methods of circular RNA discovery are RNA sequencing of rRNA and linear RNA depletion from total RNA, containing a large library of circRNAs. Detection and qualification of circRNAs to verify are also by northern blotting, RT-PCR, RT-qPCR, droplet digital PCR, NanoString nCounter, and in situ hybridization. Bioinformatic methods such as the CIRI2 algorithm still require validation of annotations ^[1]. Further research of circRNA undercovers important functions in changing the protein function, acting as a molecular marker, and, finally, harboring a potential for novel drug development.

The mechanism of action of circRNA

The circular RNAs remain a largely undiscovered group of molecules. The research findings suggest that the main mechanisms of action are inhibitory against proteins or microRNA, protein function regulation, or being translated into specific peptides. The most described in literature mechanism is “sponging” microRNAs and inhibiting miRNA activity. Circular RNAs are thought to have complementary sequences allowing binding to mRNAs and impacting translation. As circRNAs consist of noncoding sequences, they were considered “junk” DNA that resulted from faulty splicing, but there is increasing evidence that circRNA exhibits important biological functions.

Conclusion

Circular RNAs are the new class of RNA molecules with a multitude of proposed functions and potential applications. The improvements in RNA sequencing and bioinformatics enables researchers to study the origin and functions of circRNAs. This class of RNAs has been studied for potential roles in disease progress, fertility, aging, and even as models for novel therapeutics development. The exact roles of circRNA remain obscure, but scientists expect different functionalities due to the covalently closed circular structure of circRNAs and properties that come with it, such as high stability.

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References

1. Ghosal S., Das S., Sen R. et al. Circ2Traits: a comprehensive database for circular RNA potentially associated with disease and traits. Front Genet, 2013 4(283).
2. Mahmoudi E, Kiltschewskij D, Fitzsimmons C, et al. Depolarization-Associated CircRNA Regulate Neural Gene Expression and in Some Cases May Function as Templates for Translation[J]. Cell, 2020, 9(1), 25.
3. Wang S, Zhang Y, Cai Q, et al.Circular RNA FOXP1 promotes tumor progression and Warburg effect in gallbladder cancer by regulating PKLR expres- sion[J].Molecular Cancer, 2019,18(1):145.