Noise Reduction by Upstream Open Reading Frames

Gene expression can be noisier than we realize. Burst transcription can be unproductive or even detrimental if not adequately controlled. Our study reveals that upstream open reading frames (uORFs) can cancel the expression noise by reducing the protein production rate. This study discloses a proactive role of uORFs widely present in 5' leader sequences of 30% to 50% of eukaryotic mRNAs. This noise-canceling activity of uORFs is important in sustaining a robust operation of the circadian clock in Arabidopsis. The uORFs in the 5' leader of the TIMING OF CAB EXPRESSION 1 (TOC1) mRNAs help to buffer a stable TOC1 protein production level, keeping the clock precise and synchronized among cells.