Dynamic assembly of a large multidomain ribozyme visualized by cryo-electron microscopy.
Shekhar Jadhav1,2, Mauro Maiorca3,4,5, Jacopo Manigrasso6,7
1European Molecular Biology Laboratory (EMBL) Grenoble, 71 Avenue des Martyrs, Grenoble, France.
Nature Communications
|November 27, 2025
Summary
This study reveals how complex RNA molecules assemble sequentially to avoid non-functional states. Key structural motifs guide this process, creating a molecular movie of RNA folding.
Area of Science:
- Structural Biology
- Molecular Biology
- Biochemistry
Background:
- Many functional RNAs depend on precise 3D structures.
- RNAs can form non-functional misfolded states ('kinetic traps') during folding.
- Sequential assembly over scaffolds is an alternative folding pathway.
Purpose of the Study:
- To elucidate the principles of RNA sequential assembly.
- To understand how RNAs avoid misfolded states.
- To visualize the assembly of a self-splicing ribozyme.
Main Methods:
- Single-particle electron cryomicroscopy (cryo-EM)
- Small-angle X-ray scattering (SAXS)
- EM-driven molecular dynamics (MD) simulations
- Structure-based mutagenesis
- Enzymatic assays
Main Results:
- Visualized the sequential multidomain assembly of a self-splicing ribozyme.
- Identified a dynamic interplay of helical subdomains in the 5'-scaffold controlling domain docking.
- Discovered conserved secondary structure motifs orchestrating conformational changes for catalytic pocket formation.
Conclusions:
- RNA sequential assembly avoids non-functional 'kinetic traps'.
- Specific structural motifs are crucial for guiding RNA folding pathways.
- Provides a near-atomic resolution molecular movie of large multidomain RNA assembly.
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