Polypeptide targeting to mitochondria
AssigneeMedical Research Council
InventorsMichal Minczuk, Monika A. Papworth, Aaron Klug
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Abstract
Methods for delivering non-mitochondrial proteins to mitochondria are provided. Also provided are nucleic acid constructs comprising a coding sequence encoding a DNA-binding polypeptide, fused to a mitochondrial targeting sequence (MTS) and a nuclear export signal (NES), and the encoded proteins. The construct successfully delivers DNA binding proteins to the mitochondrion. A chimeric methylase based on the above construct is successfully delivered to mitochondria, resulting in modification of mtDNA.
Claims13
A nucleic acid construct for the modulation of gene expression in a mitochondrion of a eukaryotic cell, said construct comprising a coding sequence encoding a zinc finger DNA-binding polypeptide comprising at least 4 zinc fingers, fused at the N-terminus to a mitochondrial targeting sequence (MTS) and at the C-terminus to a nuclear export signal (NES), wherein the zinc finger DNA-binding polypeptide is biased towards nuclear localization and use of the MTS alone results in a predominantly nuclear localization, and wherein the zinc finger DNA-binding polypeptide is heterologous to mitochondria.
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