Mechanism of mitoribosomal small subunit biogenesis and preinitiation

Area of Science:

• Molecular Biology
• Structural Biology
• Cell Biology

Background:

• Mitoribosomes are crucial for synthesizing essential bioenergetic proteins within mitochondria.
• Understanding mitoribosome assembly is key to comprehending mitochondrial function and disease.

Purpose of the Study:

• To elucidate the sequential assembly mechanism of the small mitoribosomal subunit (SSU).
• To reveal the roles of auxiliary factors in mitoribosome biogenesis.
• To understand how assembly intermediates transition to functional mitoribosomes.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was employed to visualize SSU assembly intermediates.
• Structural analysis of mitoribosomal subunits in complex with auxiliary proteins.

Main Results:

• A step-by-step assembly pathway for the SSU was determined, involving specific auxiliary factors like TFB1M, RBFA, and METTL15.
• The methyltransferase TFB1M and RBFA facilitate initial rRNA folding and mRNA channel blocking.
• METTL15 promotes further rRNA maturation and conformational changes, allowing early binding of initiation factor mtIF3.
• The unique mitochondrial ribosomal protein mS37 displaces RBFA, completing assembly and linking it to translation initiation via mtIF3 and mtIF2.

Conclusions:

• The study reveals a dynamic and factor-modulated assembly process for the human mitoribosomal SSU.
• The protein mS37 plays a critical role in connecting SSU assembly with translation initiation.
• This work provides fundamental insights into the biogenesis of the catalytic human mitoribosome.