Mettl15-Mettl17 modulates the transition from early to late pre-mitoribosome
Status PubMed-not-MEDLINE Language English Country United States Media electronic
Document type Journal Article, Preprint
Grant support
R35 GM153502
NIGMS NIH HHS - United States
PubMed
39896671
PubMed Central
PMC11785013
DOI
10.1101/2024.12.18.629302
PII: 2024.12.18.629302
Knihovny.cz E-resources
- Publication type
- Journal Article MeSH
- Preprint MeSH
The assembly of the mitoribosomal small subunit involves folding and modification of rRNA, and its association with mitoribosomal proteins. This process is assisted by 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, but the mechanism of transition between the two was unclear. 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 ultimately 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, and present a structural data resource for understanding molecular adaptations of assembly factors in mitoribosome.
Center for Theoretical Biological Physics Northeastern University Boston MA 02115 USA
Department of Physics Northeastern University Boston MA 02115 USA
Department of Zoology Faculty of Science Charles University Prague Czech Republic
Faculty of Science University of South Bohemia 37005 České Budějovice Czech Republic
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