Circadian Rhythms in the development of spores in the fungus Neurospora crassa

Current research in the Bell-Pedersen lab uses molecular, biochemical, genetic, and genomic tools to understand how circadian oscillators control rhythmic gene expression and protein production that are critical to critical to human health and drug metabolism. We are addressing a longstanding puzzle – the existence of proteins that show robust circadian rhythms in their levels despite no rhythm in the levels of the corresponding mRNAs. We discovered that most of this regulation is due to clock control of mRNA translation. We showed that the clock in Neurospora crassa regulates daily rhythms in the activity of the conserved translation initiation factor eIF2a and elongation factor eEF2 that accounts for more than half of rhythmic translation. We also discovered a novel mechanism for rhythmic mRNA translation that involves clock control of ribosome composition and function. In addition, while it was thought that cells always maintain the highest possible translation fidelity, we found that stop codon readthrough, and thus translation fidelity, is clock-controlled, and that this depends on the composition of the ribosome. We also found that the clock controls the levels of tRNA synthetases that are critical to translation and translation fidelity. Importantly, aging is associated with both reduced circadian rhythm amplitude and decreased translation fidelity. An exciting outcome of this work is the potential that increasing circadian amplitude could improve translation fidelity and slow down the aging process.

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