Localization of human RNase Z isoforms: dual nuclear/mitochondrial targeting of the ELAC2 gene product by alternative translation initiation

PLoS One. 2011 Apr 29;6(4):e19152. doi: 10.1371/journal.pone.0019152.


RNase Z is an endonuclease responsible for the removal of 3' extensions from tRNA precursors, an essential step in tRNA biogenesis. Human cells contain a long form (RNase Z(L)) encoded by ELAC2, and a short form (RNase Z(S); ELAC1). We studied their subcellular localization by expression of proteins fused to green fluorescent protein. RNase Z(S) was found in the cytosol, whereas RNase Z(L) localized to the nucleus and mitochondria. We show that alternative translation initiation is responsible for the dual targeting of RNase Z(L). Due to the unfavorable context of the first AUG of ELAC2, translation apparently also starts from the second AUG, whereby the mitochondrial targeting sequence is lost and the protein is instead routed to the nucleus. Our data suggest that RNase Z(L) is the enzyme involved in both, nuclear and mitochondrial tRNA 3' end maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line
  • Cell Nucleus / metabolism*
  • Codon
  • Cytosol / metabolism
  • DNA, Complementary / metabolism
  • DNA, Mitochondrial / genetics
  • Endoribonucleases / chemistry*
  • Humans
  • Microscopy, Fluorescence / methods
  • Mitochondria / metabolism*
  • Molecular Sequence Data
  • Neoplasm Proteins / metabolism*
  • Plasmids / metabolism
  • Protein Biosynthesis*
  • Protein Isoforms
  • Sequence Homology, Nucleic Acid


  • Codon
  • DNA, Complementary
  • DNA, Mitochondrial
  • ELAC2 protein, human
  • Neoplasm Proteins
  • Protein Isoforms
  • Endoribonucleases
  • RNase Z