Binding to G-quadruplex RNA activates the mitochondrial GTPase NOA1

Area of Science:

• Mitochondrial biology
• Molecular genetics
• Biochemistry

Background:

• Nol1p (NOA1) is a nuclear-encoded GTPase vital for mitochondrial function and cellular survival.
• NOA1's role in mitochondrial ribosome assembly and OXPHOS regulation relies on its GTPase activity.
• No known ligands regulate NOA1's GTPase activity, hindering a full understanding of its function.

Purpose of the Study:

• To identify nucleic acids that bind to the RNA-binding domain of NOA1.
• To investigate potential regulators of NOA1's GTPase activity.

Main Methods:

• Systemic Evolution of Ligands by EXponential Enrichment (SELEX) was performed.
• Recombinant mouse wildtype NOA1 and a GTPase mutant (NOA1-K353R) were used.
• Oligonucleotide binding and GTPase activity assays were conducted.

Main Results:

• NOA1 specifically binds to oligonucleotides that form G-quadruplex structures.
• Binding of G-quadruplex oligonucleotides significantly stimulates NOA1's GTPase activity.
• A specific interaction between NOA1 and G-quadruplexes was confirmed.

Conclusions:

• NOA1 directly interacts with G-quadruplex nucleic acids.
• G-quadruplex binding acts as a positive regulator of NOA1's GTPase activity.
• This suggests a novel regulatory mechanism involving G-quadruplex RNAs in mitochondrial ribosome biogenesis.