Circular RNA (circRNA) molecules have emerged as a fascinating class of non-coding RNA molecules, which have gained significant attention from researchers since 2012. These RNA molecules are characterized by their unique ring-like structure, which is formed by covalent bonding. Unlike linear RNAs, circRNAs lack a 5′ terminal cap and a 3′ terminal poly(A) tail and are thus considered distinct from their linear counterparts.

One distinguishing feature of circRNA over linear RNA is the reverse shearing method used to create the circular structure. Rather than connecting the exons end-to-end, as is the case with linear RNAs, circRNAs utilize a tail-to-head attachment method to form the circular bonding.

Another key feature of circRNAs is their stability. Due to the covalent closed-loop structure, circRNAs tend to resist degradation by nucleic acid exonucleases, making them more stable in vitro and in vivo. This allows circRNAs to persist longer, potentially playing crucial roles in a wide range of biological processes.

During the selective splicing process, covalently closed exonic circRNAs are formed when the 3′ end of an exon of a gene binds to the same exon or to the 5′ end of its adjacent exon. However, it is important to note that circRNAs can be formed from various regions of a gene, including introns, spacers, and non-transcribed regions. Through a process called “back splicing,” these regions can form closed circular structures, leading to the creation of three types of circRNAs: exonic circular RNAs (EciRNAs), exon-intron circular RNAs (EIciRNAs), and intronic circular RNAs (ciRNAs).

The significance of circRNAs is increasingly being recognized due to their diverse functions, including regulation of gene expression, modulation of protein interactions, and even serving as potential biomarkers for various diseases. Researchers continue to explore the unique properties and functions of circRNAs, highlighting the need for further study in this intriguing area of non-coding RNA research.

Roles of circRNAs: An In-Depth Look

Circular RNAs (circRNAs) have recently emerged as crucial non-coding RNA molecules that are involved in a myriad of biological processes. Their distinctive structure and function provide a new dimension for cellular diversification and regulation, which is closely related to gene expression regulation, cellular signaling, and disease development.

• Competitive Endogenous RNA Mechanism (ceRNA Mechanism): CircRNAs are rich in multiple miRNA binding sites, making them successful miRNA sponges. By adsorbing and regulating the activity of specific miRNAs, circRNA affects the regulation of miRNA’s target genes, providing a vital role in gene regulation.
• Regulation of Transcription: It has been found that select circRNAs are able to interact with transcription factors or RNA-binding proteins, which in turn affects chromatin’s structure and transcription factor activity, leading to regulation of gene expression. This critical mechanism is involved in the delicate regulation of gene expression.
• Protein Regulation: CircRNAs can act as protein “sponges,” interacting with proteins to regulate their stability and function. This mechanism is similar to that of circRNAs acting as protein-protein and protein-nucleic acid interaction participants.
• Translation Role: CircRNAs can initiate protein translation with the help of Internal Ribosome Entry Site (IRES) in a non-cap structure-dependent manner. Additionally, circRNA methylation modification (m6A) can drive circRNA translation to synthesize proteins. CircRNAs have also been found to utilize other sequence elements, such as IRES-like elements, to initiate translation.
• Disease Association: Recent studies have shown circRNAs being important in the onset and progression of a variety of diseases, including tumors, cardiovascular diseases, and neurological disorders. CircRNAs may influence disease pathogenesis by affecting cellular metabolism, signaling, and gene expression, among others.

Outstanding Potential of circRNAs as Clinical Diagnostic Markers and Therapeutic Targets

The rise of mRNA therapeutics has been gaining momentum amidst the current COVID-19 pandemic. However, this mode of treatment has limitations due to its instability, which restricts its therapeutic potential. As an alternative, circular RNAs (circRNAs) have emerged as a promising frontier in the field of medical research. Their unique structure and specific features have revealed their potential as biomarkers for diagnostic purposes and targeted therapeutics for various diseases.

As biomarkers, circRNAs have demonstrated a correlation with the onset and progression of different pathologies, ranging from cancer to cardiovascular and neurological disorders. Their abundance, specificity, conservatism, and stability render them highly detectable in various biological samples and cells, including saliva and blood, which makes them ideal for early detection, diagnosis, and prognosis assessment of illnesses. Moreover, despite being generated differently, some circRNA sequence regions are conserved across species. For instance, homologous genes in mice and humans exhibit 5-30% similar conserved circRNAs.

CircRNAs have also gained traction as therapeutic targets and in drug development. As researchers have unveiled their mechanism of action in specific diseases, circRNAs have emerged as potential targets for therapeutic interventions and drug development. They can be modulated to interfere with specific functions related to targeted diseases, making them a valuable alternative in drug development. Additionally, circRNAs carry sequences that can be used to develop drug-carrying nanoparticles, expanding their applications in drug delivery.

Lastly, circRNAs have also shown promise as tools for gene editing and therapy. With the advent of gene-editing technology such as CRISPR-Cas, it is possible to target and modify the sequence or structure of circRNAs to modulate their function. They can also serve as a vehicle for carrying specific sequences required to promote the expression of target genes. This unparalleled potential makes circRNAs an invaluable asset to the medical research community, opening new paths in clinical diagnostics and therapeutics.

Synbio Technologies Empowers CircRNA Research with Customizable RNA Synthesis Platform

The study of circular RNA (circRNA) is a rapidly evolving field that offers immense potential for breakthroughs in medicine and biological sciences. Despite its emerging importance, circRNA remains largely understudied, necessitating continued research to unlock its full potential. Through its efficient and customizable RNA synthesis platform, Synbio Technologies is empowering researchers to explore the intricacies of circRNA with unprecedented precision and flexibility.

Synbio Technologies is a leader in synthetic biology, with a team of experts devoted to optimizing RNA sequences by taking into account factors such as codon preference, mRNA secondary structure, GC content, and translation efficiency. Utilizing advanced bioinformatics and deep learning algorithms, Synbio Technologies designs high-quality RNA sequences that enhance protein expression, solubility, and overall performance.

The RNA products offered by Synbio Technologies are fully customizable, including variable lengths, specifications, modifications, and labeling. This flexibility enables researchers to develop RNA molecules that are tailored to their specific research needs and objectives. Furthermore, these high-quality RNA products are ideal for gene function analysis and the development of therapeutic strategies.

Synbio Technologies is at the forefront of RNA synthesis technology, driving forward the development of personalized therapies and diagnostics for precision medicine. By harnessing the power of RNA sequencing, researchers can develop treatments and diagnostics based on individuals’ unique genetic and molecular profiles. This more targeted and efficient approach to patient care is the future of precision medicine.

As our understanding of circRNA’s functions, regulatory mechanisms, and associations with diseases deepens, new possibilities are emerging for disease diagnosis, treatment, and drug development. Synbio Technologies is committed to advancing the study of circRNA by providing pioneering RNA products and services that enable researchers to unlock the mysteries of this promising field. Through continued collaboration with peers and dedication to cutting-edge research and technology, Synbio Technologies is poised to make a significant contribution to the future of medicine and biological sciences.

References

[1] Meng, S., Zhou, H., Feng, Z. et al. CircRNA: functions and properties of a novel potential biomarker for cancer. Mol Cancer 2017; 16, 94.

[2] Wei-Yi Z; Ze-Rong C; Jia L. et al. Circular RNA: metabolism, functions and interactions with proteins. Molecular Cancer. 2020; 19(1), 172.

[3] Chen, X. et al.Circular RNAs in immune responses and immune diseases. Theranostics. 2019; 9,588–607.

[4] Liu CX, Chen LL. Circular RNAs: Characterization, cellular roles, and applications. Cell. 2022 9;185(12):2016-2034.