Myg1 exonuclease couples the nuclear and mitochondrial translational programs through RNA processing

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Eukaryotic cells require nuclear-mitochondrial coordination for semi-autonomous mitochondrial function.
• RNA species regulate mitochondrial processes, but key regulatory components remain largely unknown.
• Understanding nucleo-mitochondrial crosstalk is crucial for cellular homeostasis.

Purpose of the Study:

• To identify and characterize conserved proteins involved in nucleo-mitochondrial RNA processing.
• To elucidate the role of the dually localized protein Myg1 in selective RNA processing.
• To investigate the function of Myg1 in both the nucleolus and mitochondrial matrix.

Main Methods:

• Utilized mouse melanoma cells and Saccharomyces cerevisiae knockout strains complemented with human Myg1.
• Employed imaging and sub-cellular fractionation to determine Myg1 localization.
• Developed Silexoseqencing to map RNAse activity at single-nucleotide resolution.

Main Results:

• Identified Myg1 as a widely conserved 3'-5' RNA exonuclease with dual localization in the nucleolus and mitochondrial matrix.
• Demonstrated Myg1's role in processing pre-ribosomal RNA in the nucleolus, impacting cytoplasmic translation.
• Showed Myg1 processes mitochondrial RNA (ribosomal and messenger) in the mitochondrial matrix, controlling mitochondrial protein translation.
• Established a molecular link between Myg1 and the depigmenting disorder vitiligo.

Conclusions:

• Myg1 is a key, evolutionarily conserved ribonuclease coordinating nucleo-mitochondrial crosstalk.
• Myg1 regulates RNA processing in spatially distinct organelles, impacting ribosome biogenesis and protein synthesis.
• The findings provide insights into the molecular mechanisms underlying organellar communication and disease.