Our Research:circRNAs

circRNAs: an emerging RNA world

Circular RNAs are single‑stranded transcripts whose 5′ and 3′ ends are covalently joined, forming a continuous loop.
Because they lack free ends, circRNAs are:

• Exceptionally stable – many persist for days or even weeks in vivo.

• Produced by back‑splicing – the spliceosome ligates an upstream 3′ splice site to a downstream 5′ splice site, often promoted by inverted repeats or specific RNA‑binding proteins. In some loci, circRNA formation directly competes with canonical splicing and therefore tunes linear mRNA output .

• Abundant in brain and aging tissues, high‑throughput sequencing shows thousands of circRNAs accumulate in neurons with age, suggesting they may act as long‑term molecular “memories” of cellular states.

• Functionally versatile

  1. **Gene regulation in cis and trans ** – work from our lab and others showed that circRNAs can sequester RNA‑binding proteins, sponge microRNAs, or feed back on their host genes, shaping transcriptional and post‑transcriptional landscapes.

  2. **Protein coding potential ** – work from tour lab and others demonstrated that a subset of endogenous circRNAs generate proteins, expanding the functional genome beyond linear transcripts.

  3. **Biomarkers and disease links ** – altered circRNA profiles have been reported in neurodegenerative disorders, cancer, and metabolic disease; their stability makes them attractive diagnostic candidates.

Kadener Lab angle: We develop genetic, biochemical and computational tools to map circRNA biogenesis, decode their functions in neurons, and test how modulating specific circRNAs impacts behavior, aging and neurodegeneration.