# Mechanism of mitoribosomal small subunit biogenesis and preinitiation

## TL;DR

This study reveals how mitoribosomal small subunits are assembled step-by-step and how this process connects to the start of protein synthesis in mitochondria.

## Contribution

The paper presents a novel sequential mechanism of mitoribosomal small subunit biogenesis and its link to translation initiation.

## Key findings

- TFB1M binds to partially unfolded rRNA h45, facilitated by RBFA, blocking the mRNA channel.
- METTL15 promotes rRNA maturation and a conformational change in RBFA, enabling mtIF3 to bind.
- mS37 outcompetes RBFA to complete the SSU–mS37–mtIF3 complex, linking assembly to initiation.

## Abstract

Mitoribosomes are essential for the synthesis and maintenance of bioenergetic proteins. Here we use cryo-electron microscopy to determine a series of the small mitoribosomal subunit (SSU) intermediates in complex with auxiliary factors, revealing a sequential assembly mechanism. The methyltransferase TFB1M binds to partially unfolded rRNA h45 that is promoted by RBFA, while the mRNA channel is blocked. This enables binding of METTL15 that promotes further rRNA maturation and a large conformational change of RBFA. The new conformation allows initiation factor mtIF3 to already occupy the subunit interface during the assembly. Finally, the mitochondria-specific ribosomal protein mS37 (ref. 1) outcompetes RBFA to complete the assembly with the SSU–mS37–mtIF3 complex2 that proceeds towards mtIF2 binding and translation initiation. Our results explain how the action of step-specific factors modulate the dynamic assembly of the SSU, and adaptation of a unique protein, mS37, links the assembly to initiation to establish the catalytic human mitoribosome.

Structural analysis of several small mitoribosomal subunit intermediates reveals a sequential mechanism of biogenesis, and how assembly links to initiation to form active mitoribosomes.