bims-mitran 2024-06-09 papers

Issue of 2024–06–09
two papers selected by
Andreas Kohler, Umeå University

FEBS Open Bio. 2024 Jun 07.

Mitochondrial ribosome biogenesis and redox sensing.

Michele Brischigliaro, Ana Sierra-Magro, Ahram Ahn, Antoni Barrientos.

Mitoribosome biogenesis is a complex process involving RNA elements encoded in the mitochondrial genome and mitoribosomal proteins typically encoded in the nuclear genome. This process is orchestrated by extra-ribosomal proteins, nucleus-encoded assembly factors, which play roles across all assembly stages to coordinate ribosomal RNA processing and maturation with the sequential association of ribosomal proteins. Both biochemical studies and recent cryo-EM structures of mammalian mitoribosomes have provided insights into their assembly process. In this article, we will briefly outline the current understanding of mammalian mitoribosome biogenesis pathways and the factors involved. Special attention is devoted to the recent identification of iron-sulfur clusters as structural components of the mitoribosome and a small subunit assembly factor, the existence of redox-sensitive cysteines in mitoribosome proteins and assembly factors, and the role they may play as redox sensor units to regulate mitochondrial translation under stress.

Keywords: iron–sulfur cluster; mitochondrial disease; mitochondrial ribosome; mitochondrial translation; mitoribosome assembly; redox sensing

DOI: https://doi.org/10.1002/2211-5463.13844

Nat Commun. 2024 Jun 01. 15(1): 4683

Structural basis for human mitochondrial tRNA maturation.

Vincent Meynier, Steven W Hardwick, Marjorie Catala, Johann J Roske, Stephanie Oerum, Dimitri Y Chirgadze, Pierre Barraud, Wyatt W Yue, Ben F Luisi, Carine Tisné.

The human mitochondrial genome is transcribed into two RNAs, containing mRNAs, rRNAs and tRNAs, all dedicated to produce essential proteins of the respiratory chain. The precise excision of tRNAs by the mitochondrial endoribonucleases (mt-RNase), P and Z, releases all RNA species from the two RNA transcripts. The tRNAs then undergo 3'-CCA addition. In metazoan mitochondria, RNase P is a multi-enzyme assembly that comprises the endoribonuclease PRORP and a tRNA methyltransferase subcomplex. The requirement for this tRNA methyltransferase subcomplex for mt-RNase P cleavage activity, as well as the mechanisms of pre-tRNA 3'-cleavage and 3'-CCA addition, are still poorly understood. Here, we report cryo-EM structures that visualise four steps of mitochondrial tRNA maturation: 5' and 3' tRNA-end processing, methylation and 3'-CCA addition, and explain the defined sequential order of the tRNA processing steps. The methyltransferase subcomplex recognises the pre-tRNA in a distinct mode that can support tRNA-end processing and 3'-CCA addition, likely resulting from an evolutionary adaptation of mitochondrial tRNA maturation complexes to the structurally-fragile mitochondrial tRNAs. This subcomplex can also ensure a tRNA-folding quality-control checkpoint before the sequential docking of the maturation enzymes. Altogether, our study provides detailed molecular insight into RNA-transcript processing and tRNA maturation in human mitochondria.

DOI: https://doi.org/10.1038/s41467-024-49132-0