Exploring Circular RNAs: The Challenges and Wonders of RNA’s Unique Structure 

Circular RNAs (circRNAs) have transformed from being dismissed as splicing errors to promising players in the world of biology and medicine. Found across the tree of life, these unique RNA molecules form loops through an atypical splicing process, known as back-splicing. Despite their low abundance—making up only about 0.1% of non-ribosomal RNAs—circRNAs hold immense potential as biomarkers and therapeutic agents for conditions like cancer, cardiovascular diseases, and Alzheimer’s. 

Challenges and Advances in circRNA Research 

CircRNAs are notoriously tricky to study because their circular structure makes them nearly indistinguishable from linear RNAs produced from the same genomic regions. Researchers need to specifically identify the “back-splice junctions” that define these molecules. Sequencing, while helpful, requires optimized methods to exclude ribosomal RNA and focus on circular forms. Techniques like RNase R digestion, custom algorithms for junction detection, and synthetic controls (e.g., SynCRS) are helping researchers overcome these hurdles. 

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