Features and biomedical relevance of circular RNA biogenesis

Circular RNAs (circRNAs) are natural outputs of transcription and RNA processing in eukaryotes. Four subclasses of circRNAs have been identified in animal cells, and most circRNAs are generated via backsplicing. The intricate formation of circRNAs is orchestrated by various cis-regulatory elements and trans-acting factors. Previous studies have gained insights into the general factors and elements involved in backsplicing. Recently, modulation of circRNA biogenesis to generate tissue-specific expression patterns is coming into focus. We summarize various mechanisms involved in the biogenesis of distinct circRNA subclasses across multiple cell types. We also discuss the involvement of relevant mechanisms in human diseases and potential biomedical interventions that target circRNA pathways.