Ribonuclease RNase Z is an evolutionarily conserved deAMPylase

Area of Science:

• Biochemistry
• Molecular Biology
• Cellular Metabolism

Background:

• Protein AMPylation is a conserved posttranslational modification where adenosine monophosphate (AMP) attaches to proteins.
• Mitochondrial AMPylase, Selenoprotein O (SelO), regulates metabolism and oxidative stress via protein AMPylation.
• The enzyme responsible for removing AMP from modified proteins was previously unknown.

Purpose of the Study:

• To identify the enzyme that catalyzes deAMPylation of AMPylated protein substrates.
• To elucidate the role of this enzyme in the reversible AMPylation pathway.
• To understand the broader biological significance of RNase Z.

Main Methods:

• Biochemical assays to test deAMPylation activity.
• Enzyme kinetics studies.
• In vitro and in vivo functional assays.

Main Results:

• Ribonuclease Z (RNase Z) was identified as the enzyme responsible for deAMPylation.
• RNase Z is both necessary and sufficient to remove AMP from AMPylated substrates.
• This establishes RNase Z as a moonlighting enzyme with a novel function beyond tRNA processing.

Conclusions:

• RNase Z catalyzes deAMPylation, revealing its role in reversible protein AMPylation.
• The discovery highlights the importance of AMPylation as a regulatory mechanism, similar to phosphorylation.
• RNase Z possesses a previously unrecognized biological function, expanding its known significance.