HEPN RNases - an emerging class of functionally distinct RNA processing and degradation enzymes

Area of Science:

• Molecular Biology
• Enzymology
• Biochemistry

Background:

• HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding) RNases represent a functionally diverse and emerging class of enzymes.
• These enzymes are characterized by a conserved α-helical bundle containing a short consensus RNase motif.

Purpose of the Study:

• To summarize the canonical elements of the HEPN RNase family.
• To identify molecular features governing HEPN RNase function and regulation.
• To explore mechanisms of HEPN RNase activation and inhibition.

Main Methods:

• Comparative analysis of conserved HEPN fold and surrounding structural organizations.
• Review of known bacterial and eukaryotic HEPN RNase examples (e.g., CRISPR-Cas, toxin-antitoxin systems).
• Examination of dimerization-dependent catalytic center formation.

Main Results:

• HEPN RNase activation universally requires dimerization, positioning conserved motifs at the dimer interface for a composite catalytic center.
• Structural variations around the conserved HEPN dimer enable specialized functions.
• The HEPN RNase family is conserved across evolution, found in both prokaryotes and eukaryotes.

Conclusions:

• HEPN RNases exhibit conserved core structures but diverse functional adaptations.
• Dimerization is a key regulatory mechanism for HEPN RNase activity.
• Understanding HEPN RNase structure-function relationships is crucial for elucidating RNA metabolism and regulation.