PNPASE regulates RNA import into mitochondria

Area of Science:

• Mitochondrial biology
• Molecular genetics
• RNA processing

Background:

• RNA import into mammalian mitochondria is crucial for mitochondrial genome expression.
• The mechanisms and factors governing mitochondrial RNA import remain largely unknown.
• Polynucleotide phosphorylase (PNPASE) was previously localized to the mitochondrial intermembrane space.

Purpose of the Study:

• To investigate the role of PNPASE in the import of nuclear-encoded RNAs into the mitochondrial matrix.
• To elucidate the function of PNPASE in mitochondrial RNA regulation.

Main Methods:

• Localization studies of PNPASE within mitochondria.
• Analysis of mitochondrial RNA processing and import upon PNPASE reduction.
• Identification of interactions between PNPASE and imported RNAs.
• Isolation of a mitochondrial RNA targeting signal.

Main Results:

• PNPASE reduction led to impaired mitochondrial RNA processing and accumulation of polycistronic transcripts.
• The import of specific RNAs (RNase P, 5S rRNA, MRP RNAs) was dependent on PNPASE expression.
• PNPASE demonstrated separable RNA processing and import activities.
• A novel mitochondrial RNA targeting signal was identified, facilitating PNPASE-dependent RNA import.

Conclusions:

• PNPASE plays a critical, previously unrecognized role in mediating the translocation of nuclear-encoded RNAs into the mitochondrial matrix.
• PNPASE functions in both RNA processing and import, suggesting a dual role in mitochondrial RNA regulation.
• The findings uncover a new pathway for RNA import into mitochondria, highlighting PNPASE as a key regulator.