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Updated: Sep 9, 2025

Single Molecule Fluorescence Energy Transfer Study of Ribosome Protein Synthesis
Published on: July 6, 2021
Mettl15-Mettl17 modulates the transition from early to late pre-mitoribosome
Yury Zgadzay1, Claudio Mirabello2, George Wanes3
1Department of Integrative Structural Biology, Institute of Genetics and Molecular and Cellular Biology, University of Strasbourg, Illkirch, France.
Abstract:
The biogenesis of the mitoribosomal small subunit involves a dynamic network of assembly factors. Conserved methyltransferases Mettl15 and Mettl17 act on the solvent-exposed surface of rRNA. Binding of Mettl17 is associated with the early assembly stage, whereas Mettl15 is involved in the late stage. Here, we integrate structural data from Trypanosoma brucei with mammalian homologs and molecular dynamics simulations. We reveal how the interplay of Mettl15 and Mettl17 in intermediate steps links the distinct stages of small subunit assembly. The analysis suggests a model wherein Mettl17 acts as a platform for Mettl15 recruitment. Subsequent release of Mettl17 allows a conformational change of Mettl15 for substrate recognition. Upon methylation, Mettl15 adopts a loosely bound state which leads to its replacement by initiation factors, concluding the assembly. Together, our results indicate that assembly factors Mettl15 and Mettl17 cooperate to regulate the biogenesis process.
Insights
Methyltransferases Mettl15 and Mettl17 cooperate to regulate mitochondrial ribosomal small subunit biogenesis. Their interplay links early and late assembly stages, ensuring proper ribosome formation.
Area of Science:
- Molecular Biology
- Biochemistry
- Cell Biology
Background:
- Mitochondrial ribosomal small subunit (SSU) biogenesis is crucial for cellular respiration.
- Assembly factors, including methyltransferases Mettl15 and Mettl17, guide this complex process.
- These factors act at distinct stages, but their precise coordination remains unclear.
Purpose of the Study:
- To elucidate the cooperative mechanism of methyltransferases Mettl15 and Mettl17 in mitoribosomal SSU biogenesis.
- To integrate structural and dynamic data to model their interplay during assembly.
- To understand how these factors link early and late stages of SSU formation.
Main Methods:
- Integration of structural data from Trypanosoma brucei and mammalian homologs.
- Molecular dynamics simulations to analyze protein-rRNA interactions and conformational changes.
- Biochemical assays to determine the roles of Mettl15 and Mettl17 in distinct assembly steps.
Main Results:
- Mettl17 binds early in assembly, potentially serving as a platform for Mettl15 recruitment.
- Mettl15 is involved in later stages, with its activity dependent on Mettl17 release and conformational changes.
- The sequential action and interplay of Mettl15 and Mettl17 facilitate the transition between assembly stages and final maturation.
Conclusions:
- Mettl15 and Mettl17 function cooperatively to regulate mitoribosomal SSU biogenesis.
- Their dynamic interplay ensures the ordered progression and completion of ribosome assembly.
- This study provides a mechanistic model for the coordinated action of these essential assembly factors.
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