Structure and activity of the only human RNase T2

Area of Science:

• Biochemistry
• Structural Biology
• Neuroscience

Background:

• Mutations in the human RNase T2 gene are linked to white matter disease, characterized by brain abnormalities and neurological symptoms.
• The precise pathomechanism of RNase T2 deficiency remains unclear, despite its known association with neurological disorders.
• Human RNase T2 is the sole member of the Rh/T2/S family of acidic hydrolases and exhibits tumor-suppressing properties independent of its catalytic activity.

Purpose of the Study:

• To determine the X-ray structure of human RNase T2.
• To analyze the catalytic features of RNase T2 in the presence of bivalent cations.
• To investigate the structural consequences of known clinical mutations in RNase T2.

Main Methods:

• X-ray crystallography at 1.6 Å resolution.
• Structural analysis of human RNase T2.
• Biochemical assays to analyze catalytic features and mutation effects.

Main Results:

• The X-ray structure of human RNase T2 was determined at 1.6 Å resolution.
• The core fold of human RNase T2 is similar to plant T2 RNases, but external loops show distinct differences.
• Analysis provided insights into catalytic features and the structural impact of clinical mutations.

Conclusions:

• The determined structure provides a foundation for understanding human RNase T2 function.
• The findings may elucidate the enzyme's mode of action, including non-catalytic functions.
• This structural information could aid in understanding RNase T2 deficiency-related diseases.