• Post-Transcriptional Tuning of the Clock: While the transcriptional loop sets the rhythm, the Kadener Lab discovered that post-transcriptional regulation (after RNA is made) plays a crucial role in fine-tuning the clock’s precision. This includes mechanisms like splicing, RNA editing, translation, and RNA decay. These regulatory layers help ensure the clock remains robust under changing environmental and physiological conditions.

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• miRNAs Are Essential for Clock Function: A major discovery from the lab showed that microRNAs (miRNAs) — small regulatory RNAs — are indispensable for circadian timing. In a foundational 2009 study, the team found that flies lacking Dicer-1 (an enzyme needed for miRNA production) exhibit severe rhythm disruptions. One key miRNA, bantam, directly targets the Clk gene’s long 3′UTR to suppress CLK protein levels. Overexpression of bantam lengthens the circadian period, while removing its target sites leads to unstable rhythms and neuronal defects. These findings highlight miRNAs as key “fine-tuners” that keep the clock running smoothly.

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• The Clock Adapts to Temperature: The lab also revealed that the circadian system is more flexible than previously thought. In a 2019 eLife study, they discovered that the timeless (tim) gene undergoes temperature-sensitive alternative splicing:
  - At cold temperatures (18°C), flies produce novel isoforms like tim-cold and tim-short&cold, leading to reduced TIM protein and a slower clock
  - At warm temperatures (29°C), a different isoform (tim-medium) is upregulated.
  These temperature-dependent splice forms help the clock adapt to environmental conditions. Blocking them impairs normal behavior, suggesting the splicing machinery acts as a molecular thermometer.