Kadener Lab
Our Research
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:
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Exceptionally stable – many persist for days or even weeks in vivo.
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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 .
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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.
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Functionally versatile
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**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.
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**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.
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**Biomarkers and disease links ** – altered circRNA profiles have been reported in neurodegenerative disorders, cancer, and metabolic disease; their stability makes them attractive diagnostic candidates.
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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.
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Circadian Rhythms: keeping time, from molecules to behavior
Circadian rhythms are ~24‑hour cycles in physiology and behavior that let organisms anticipate daily environmental changes. A conserved transcription‑translation feedback loop underlies these rhythms, but post‑transcriptional regulation (alternative splicing, RNA stability, translation control) is now recognized as also crucial.
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Core molecular clock – in Drosophila, CLOCK (CLK) and CYCLE (CYC) drive rhythmic transcription of period (per) and timeless (tim); PER/TIM proteins feed back to repress CLK/CYC, closing the loop.
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RNA‑level fine‑tuning – miRNAs, RNA‑binding proteins and splice factors shape clock mRNA abundance and isoform choice, buffering noise and enabling environmental adaptation. For example, tight 3′‑UTR control of Clk“denoises” rhythms, ensuring each individual fly maintains a robust behavioral period.
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Temperature and light entrainment – beyond transcriptional effects, the clock senses ambient temperature and photoperiod through RNA processing events that adjust protein isoforms and translation rates.