Abstract
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Highlights
Circadian rhythms allow organisms to orchestrate behavioral and physiological outputs in anticipation of predictable diurnal changes in the environment
Pre-mRNA splicing factor four is a new regulator of the circadian clock
We identify a novel alternative splicing (AS) mechanism that affects the pace of endogenous circadian oscillations and implicates pre-mRNA processing 4 (PRP4) and other tri-snRNP components in circadian clock regulation
Summary
Circadian rhythms allow organisms to orchestrate behavioral and physiological outputs in anticipation of predictable diurnal changes in the environment These rhythms are generated by endogenous molecular clocks that entrain to environmental cycles, predominantly light and temperature, and can maintain rhythms when released into constant conditions (free-run). A conserved mechanistic feature of circadian clocks is an auto-regulatory transcriptional feedback loop in which circadian proteins rhythmically regulate their own expression to generate a clock, and drive a global program of cycling gene expression. We show that alternative splicing of this intron in tim represents an important mechanism to time the daily accumulation of TIM, in constant darkness following entrainment to light:dark cycles and in temperature cycles Together, these findings identify a mechanism contributing to the maintenance of clock function
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