IMPORTATION OF MITOCHONDRIAL PROTEIN BY AN ENHANCED ALLOTOPIC APPROACH

摘要

The inventors demonstrate that mRNA sorting to the mitochondrial surface is an efficient way to proceed to such an allotopic expression, and that this mRNA sorting can be controlled by selecting appropriate mitochondrion-targeting sequence (MTS) and appropriate 3'UTR sequences. The CDS sequence which codes for the protein to be delivered into the mitochondrion is guided by these appropriate MTS and 3'UTR sequences from the nuclear compartment to the mitochondrion-bound polysomes (where the CDS is translated), and aids in an efficient translocation of a mature functional protein into the mitochondria. Appropriate MTS and 3'UTR sequences correspond to those of nuclearly-transcribed mitochondrially-targeted mRNAs. The inventors demonstrate that, to obtain a stable therapeutically-effective importation, both an appropriate MTS and an appropriate 3'UTR should preferably be used.