Kadener Lab
Our Research: Circadian Rhythms
Post-transcriptional Control of the Circadian Clock
1.  Post‑transcriptional Fine‑Tuning of the Core Clock
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microRNAs as time‑keepers. Depleting Dicer‑1 in pacemaker neurons abolished locomotor rhythms; AGO‑RIP‑chip then identified clk, vri and cwo as direct miRNA targets, inaugurating miRNA control as a defining layer of the clock.
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UTR ‘denoising’. Swapping the native Clk 3′‑UTR with an SV40 tail left mean mRNA levels untouched but increased neuron‑to‑neuron variance, fragmenting behaviour. The 3′‑UTR’s miRNA sites therefore buffer transcriptional noise to keep flies in sync.
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Why it matters These studies positioned miRNAs and untranslated regions as indispensable “shock absorbers” that preserve circadian precision in a noisy cellular world.
2. Temperature‑Responsive Splicing: An RNA Thermometer
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Thermo‑switching of timeless. By performing RNA‑seq from fly heads at different temperatures we identified four tim mRNA isoforms; the cold‑specific TIM‑SC variant rescues rhythms at 18 °C, proving alternative splicing is the molecular thermometer of the fly clock. We are also now studying the role of the other temperature-regulated isoforms as well as the mechanisms regulating the splicing.
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Why it matters: One gene, multiple temperature‑tuned timers—this mechanism explains seasonal behaviour and highlights splice factors as chronomedicine targets
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