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.

PubMed

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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