Structural and evolutionary insights into the eukaryotic RNase MRP ribonucleoprotein complex.

Area of Science:

• Molecular Biology
• Structural Biology
• Evolutionary Biology

Background:

• RNase MRP is a vital eukaryotic ribonucleoprotein complex.
• Its exact composition and substrate processing mechanisms in most eukaryotes are not fully understood.
• Previous research focused mainly on yeast RNase MRP.

Purpose of the Study:

• To elucidate the composition and structure of human RNase MRP.
• To understand the evolutionary adaptations and substrate-binding mechanisms of RNase MRP.
• To determine the functional roles of RNase MRP subunits in cellular processes.

Main Methods:

• Integrative structural analysis using cryo-electron microscopy (cryo-EM).
• Structure-based bioinformatics and evolutionary dissection.
• Functional assays to assess precursor-rRNA cleavage and ribosome assembly.

Main Results:

• Identified NEPRO (RMP64) and C18orf21 (RMP24) as essential subunits unique to human RNase MRP.
• Determined the cryo-EM structure of human RNase MRP, revealing a 'double-anchor' substrate-binding mechanism.
• Demonstrated the indispensability of these subunits for precursor-rRNA cleavage, ribosome assembly, protein synthesis, and chondrogenesis.

Conclusions:

• Human RNase MRP possesses unique subunits and an evolved substrate-binding mechanism for broad specificity.
• This study provides a unified evolutionary and mechanistic framework for RNase MRP.
• The findings are critical for understanding ribosome biogenesis and related cellular functions.