Evidence for an adaptation mechanism of mitochondrial translation via tRNA import from the cytosol

Mol Cell. 2007 Jun 8;26(5):625-37. doi: 10.1016/j.molcel.2007.04.019.

Abstract

Although mitochondrial import of nuclear DNA-encoded RNAs is widely occurring, their functions in the organelles are not always understood. Mitochondrial function(s) of tRNA(Lys)(CUU), tRK1, targeted into Saccharomyces cerevisiae mitochondria was mysterious, since mitochondrial DNA-encoded tRNA(Lys)(UUU), tRK3, was hypothesized to decode both lysine codons, AAA and AAG. Mitochondrial targeting of tRK1 depends on the precursor of mitochondrial lysyl-tRNA synthetase, pre-Msk1p. Here we show that substitution of pre-Msk1p by its Ashbya gossypii ortholog results in a strain in which tRK3 is aminoacylated, while tRK1 is not imported. At elevated temperature, drop of tRK1 import inhibits mitochondrial translation of mRNAs containing AAG codons, which coincides with the impaired 2-thiolation of tRK3 anticodon wobble nucleotide. Restoration of tRK1 import cures the translational defect, suggesting the role of tRK1 in conditional adaptation of mitochondrial protein synthesis. In contrast with the known ways of organellar translation control, this mechanism exploits the RNA import pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Biological Transport, Active
  • Cytosol / metabolism
  • DNA, Fungal / genetics
  • DNA, Mitochondrial / genetics
  • Lysine-tRNA Ligase / chemistry
  • Lysine-tRNA Ligase / metabolism
  • Mitochondria / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Protein Biosynthesis*
  • RNA, Fungal / chemistry
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism
  • RNA, Transfer / genetics*
  • RNA, Transfer / metabolism*
  • RNA, Transfer, Lys / chemistry
  • RNA, Transfer, Lys / genetics
  • RNA, Transfer, Lys / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomycetales / genetics
  • Saccharomycetales / metabolism
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Temperature

Substances

  • DNA, Fungal
  • DNA, Mitochondrial
  • RNA, Fungal
  • RNA, Transfer, Lys
  • RNA, Transfer
  • Lysine-tRNA Ligase