The mechanism of Cbp1 protein-dependent COBmRNA stability in yeast mitochondria

Abstract

It has been one hundred years since mitochondria were first observed and recorded by Altman in 1890, when they were named bioblasts. Ten years later, "mitochondrion", which means threadlike granule, started to be used. It is still an unanswered question where this organelle originated. More and more evidence and enthusiasm favor the hypothesis that mitochondria have evolved from engulfed prokaryotic symbionts (Martin and Muller, 1998). An opposing idea proposed that mitochondria just represent another kind of intracellular membrane system, like Golgi (Cavalier-Smith, 1987). Whichever is true, it is known today that mitochondria are well-defined and ubiquitous cellular structures compartmentalized by double membranes. They not only provide some of their own genetic information, but also are the site of cellular lipid synthesis and oxidative phosphorylation. Since mitochondria are such complex functional units, the study of mitochondrial biogenesis (a process to produce a respiratory competent organelle) is a combined issue of genetics, biochemistry and chemistry. It aims to answer questions regarding mitochondrial morphology, continuity, protein and phospholipid syntheses, protein transport, etc. This study is concentrated on a since regulatory step of a single mitochondrial gene in yeast, i.e. the stabilization of the cytochrome b (COB) mRNA, which requires the nuclear-encoded Cbp1 protein. The results of my study support that the nuclear-encoded Cbp1 protein stabilizes COB messages in two different ways: First, it processes the 5'-untranslated region (UTR); second, it is required after formation of the mature 5'-end of COB mRNA. Evidence is provided that Cbp1 physically interacts with a CCG element in the COB 5'-UTR, and the maintenance of this interaction is critical for COB mRNA accumulation. Suppressor analysis of COB 5'-UTR mutations identified factors in general mitochondrial mRNA turnover pathways. Thus, in addition to studying the mechanism of Cbp1-dependent COB mRNA stabilization, the further analysis of genes identified by mutation in this work may reveal previously uncharacterized components in the general pathways of yeast mitochondrial mRNA decay.