WBSCR16 is essential for mitochondrial 16S rRNA processing in mammals

Area of Science:

• Mitochondrial biology
• Molecular genetics
• Metabolic regulation

Background:

• Mitochondrial ribosomal RNAs (rRNAs) are vital for gene expression and cellular energy metabolism.
• The specific proteins governing mitochondrial 16S rRNA processing are not well-characterized.

Purpose of the Study:

• To investigate the role of WBSCR16 in mitochondrial 16S rRNA processing and its impact on cellular metabolism.
• To elucidate the mechanism by which WBSCR16 influences rRNA maturation and ribosome biogenesis.

Main Methods:

• Generation and analysis of adipose-specific Wbscr16 knockout mice and cell lines.
• Biochemical assays to identify WBSCR16 as a 16S rRNA-binding protein.
• Investigating the interaction of WBSCR16 with RNase P subunit MRPP3.
• Metabolic phenotyping of Wbscr16-deficient and overexpressing models.

Main Results:

• WBSCR16 is essential for the cleavage of 16S rRNA-mt-tRNALeu, facilitating 16S rRNA processing and mitochondrial ribosome assembly.
• WBSCR16 recruits MRPP3 to nascent 16S rRNA, aiding in its maturation.
• Adipose-specific Wbscr16 deficiency leads to increased energy expenditure and obesity resistance by promoting lipid utilization in brown adipose tissue.
• WBSCR16 overexpression enhances 16S rRNA processing and promotes glucose utilization.

Conclusions:

• WBSCR16 is a key mammalian protein regulating mitochondrial 16S rRNA processing and ribosome biogenesis.
• WBSCR16 plays a critical role in balancing glucose and lipid metabolism, acting as a central regulator of energy homeostasis.