Dynamic association of human mRNP proteins with mitochondrial tRNAs in the cytosol

RNA. 2018 Dec;24(12):1706-1720. doi: 10.1261/rna.066738.118. Epub 2018 Aug 23.


Cytoplasmic localization, stability, and translation of mRNAs are controlled by their dynamic association of numerous mRNA-binding (mRNP) proteins, including cold shock domain (CSD)-containing proteins, heterogeneous nuclear ribonucleoproteins (hnRNPs), and serine/arginine-rich (SR) proteins. Here, we demonstrate that the most abundant human mRNP protein, the CSD-containing Y-box-binding protein 1 (YBX1), the closely related YBX3 protein, and other mRNP proteins, such as SRSF1, SRSF2, SRSF3, hnRNP A1, and H, specifically and efficiently interact with overlapping sets of mitochondrial tRNAs (mt tRNAs). In vitro reconstitution and in vivo binding experiments show that YBX1 recognizes the D- and/or T-stem-loop regions of mt tRNAs through relying on the RNA-binding capacity of its CSD. Cell fractionation and in vivo RNA-protein cross-linking experiments demonstrate that YBX1 and YBX3 interact with mt tRNAs in the cytosol outside of mitochondria. Cell fractionation and fluorescence in situ hybridization experiments provide evidence that mitochondrial autophagy promotes the release of mt tRNAs from the mitochondria into the cytoplasm. Association of mRNP proteins with mt tRNAs is highly dynamic; it is rapidly increased upon transcription inhibition and decreased during apoptosis. Although the cytoplasmic function of mt tRNAs remains elusive, their dynamic interactions with key mRNA-binding proteins may influence cytoplasmic mRNA stability and/or translation.

Keywords: YBX1; cold shock domain protein; mRNA-binding protein; mRNP; mitochondrial tRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / genetics
  • Cytosol / chemistry*
  • Heterogeneous Nuclear Ribonucleoprotein A1 / chemistry
  • Heterogeneous Nuclear Ribonucleoprotein A1 / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Mitochondria / chemistry*
  • Mitochondria / genetics
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • RNA, Transfer / chemistry*
  • RNA, Transfer / genetics
  • Ribonucleoproteins / chemistry*
  • Ribonucleoproteins / genetics
  • Serine-Arginine Splicing Factors / chemistry
  • Serine-Arginine Splicing Factors / genetics
  • Y-Box-Binding Protein 1 / chemistry
  • Y-Box-Binding Protein 1 / genetics


  • Heterogeneous Nuclear Ribonucleoprotein A1
  • RNA, Messenger
  • Ribonucleoproteins
  • SRSF1 protein, human
  • SRSF3 protein, human
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • messenger ribonucleoprotein
  • SRSF2 protein, human
  • Serine-Arginine Splicing Factors
  • RNA, Transfer