Stepwise maturation of the peptidyl transferase region of human mitoribosomes.

Tea Lenarčič, Mateusz Jaskolowski, Marc Leibundgut, Alain Scaiola, Tanja Schönhut, Martin Saurer, Richard G Lee, Oliver Rackham, Aleksandra Filipovska, Nenad Ban

Nature communications 2021 Jun 16

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Mitochondrial ribosomes are specialized for the synthesis of membrane proteins responsible for oxidative phosphorylation. Mammalian mitoribosomes have diverged considerably from the ancestral bacterial ribosomes and feature dramatically reduced ribosomal RNAs. The structural basis of the mammalian mitochondrial ribosome assembly is currently not well understood. Here we present eight distinct assembly intermediates of the human large mitoribosomal subunit involving seven assembly factors. We discover that the NSUN4-MTERF4 dimer plays a critical role in the process by stabilizing the 16S rRNA in a conformation that exposes the functionally important regions of rRNA for modification by the MRM2 methyltransferase and quality control interactions with the conserved mitochondrial GTPase MTG2 that contacts the sarcin-ricin loop and the immature active site. The successive action of these factors leads to the formation of the peptidyl transferase active site of the mitoribosome and the folding of the surrounding rRNA regions responsible for interactions with tRNAs and the small ribosomal subunit.

Citation

Tea Lenarčič, Mateusz Jaskolowski, Marc Leibundgut, Alain Scaiola, Tanja Schönhut, Martin Saurer, Richard G Lee, Oliver Rackham, Aleksandra Filipovska, Nenad Ban. Stepwise maturation of the peptidyl transferase region of human mitoribosomes. Nature communications. 2021 Jun 16;12(1):3671