Insights into the Translational Activation Mechanisms of the COX1 mRNA in Yeast Mitochondria

Mitochondrial translation is a critical regulatory step in mitochondrial genome expression. In Saccharomyces cerevisiae, translational activators are believed to bind to the 5 UTRs of their target mRNAs to position the mitochondrial ribosome at the start codon. Pet309 and Mss51 are translational activators of COX1 mRNA, which encodes subunit one of cytochrome c oxidase. Pet309 physically interacts with COX1 mRNA, but no direct interaction of Mss51 with its target mRNA has been detected. Currently, the mechanisms underlying translational activation of COX1, or any other mitochondrial gene, remain poorly understood. To explore in depth the mechanism of COX1 mRNA translational activation, we studied the association of Pet309 and Mss51 with the mitochondrial ribosome. Both Pet309 and Mss51 interact with the mitoribosome regardless of the presence of COX1 mRNA or of each other. Pet309s association with the ribosome and with COX1 mRNA depends on its N-terminal domain. These findings indicate that Pet309 and Mss51 stably interact with the mitoribosome independently of an active translation. By integrating our data with previously published research, we propose a new mechanism of COX1 mRNA translation activation. SUMMARY STATEMENTYeast mitochondrial mRNAs require translational activators by an almost unknown mechanism. Based on our findings on Mss51 and Pet309 function, we present a new model for translation of the COX1 mRNA