[mRNA localization to the mitochondrial surface: a tool to treat retinal pathologies due to mitochondrial DNA mutations]

Abstract

mRNA subcellular distribution and translational control are key player mechanisms for development, cellular differentiation and synaptic plasticity. mRNA localization is also implicated in mitochondria biogenesis. Two sequences within the transcripts are involved in their mitochondrial localization: the region coding for the mitochondrial targeting sequence (MTS) and the 3'UTR. Therefore, we decided to use mRNA localization as a tool to address to mitochondria a protein that is not normally imported. We have chosen to construct nuclear versions of the mtDNA encoded ATP6 and ND1 genes to which we appended the signals of COX10 gene, whose transcript is sorted to the mitochondrial surface. Thus, by directing a hybrid mRNA to the mitochondrial surface, we significantly improved the feasibility of the allotopic approach for the mitochondrial genes examined.