Circular RNAs in animals: Biogenesis, function and cell fate control

In recent years, circular RNAs (circRNAs), a class of RNA molecules characterized by a covalently closed circular structure, have emerged as a complex family of eukaryotic transcripts with distinctive biological features. Beyond their unusual structure, which generally enhances stability by eliminating free ends, circRNAs have attracted attention because their expression is often cell- and tissue-specific and many are conserved across species. These characteristics support diverse molecular functions, including regulation through interactions with microRNAs and RNA-binding proteins (RBP), and in selected contexts, protein translation. The recognition of circRNAs has therefore added an additional layer of post-transcriptional regulation and expanded our understanding of how gene expression programs are organized across cellular states. Notably, an increasing number of studies links circRNA dynamics to differentiation and development, implicating circRNAs in the regulatory logic that governs stemness maintenance and lineage commitment. In this Review, we summarize current knowledge of circRNA biogenesis and function, highlight emerging connections between circRNAs and cell fate decisions, and discuss how these insights can inform the rational development of bioengineered circRNAs as stable yet programmable platforms to steer differentiation toward targeted cell types and support future RNA-based therapeutic strategies.