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

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Cytoplasmic mRNA fate is regulated by mRNA-binding proteins (mRNPs).
• Key mRNPs include cold shock domain (CSD)-containing proteins, heterogeneous nuclear ribonucleoproteins (hnRNPs), and serine/arginine-rich (SR) proteins.
• The role of these proteins in regulating mitochondrial components is largely unexplored.

Purpose of the Study:

• To investigate the interaction between abundant human mRNP proteins and mitochondrial tRNAs (mt tRNAs).
• To determine the cellular localization and regulation of mt tRNA-mRNP complexes.
• To explore the potential functional implications of cytoplasmic mt tRNAs.

Main Methods:

• In vitro protein-RNA binding assays.
• In vivo RNA-protein cross-linking and co-immunoprecipitation.
• Cell fractionation and fluorescence in situ hybridization (FISH).
• Transcription inhibition and apoptosis induction models.

Main Results:

• Y-box-binding protein 1 (YBX1), YBX3, SRSF1, SRSF2, SRSF3, hnRNP A1, and H bind to mt tRNAs.
• YBX1 recognizes mt tRNAs via its CSD, primarily binding D- and T-stem-loop regions.
• YBX1 and YBX3 bind mt tRNAs in the cytosol, independent of mitochondrial import.
• Mitochondrial autophagy releases mt tRNAs into the cytoplasm.
• mt tRNA-mRNP interactions are dynamic, increasing with transcription inhibition and decreasing during apoptosis.

Conclusions:

• Abundant mRNP proteins, including YBX1, associate with mt tRNAs in the cytoplasm.
• Mitochondrial autophagy facilitates mt tRNA release into the cytosol.
• The cytoplasmic presence and dynamic mRNP association of mt tRNAs suggest a role in regulating cytoplasmic mRNA metabolism.