The mitoribosome-specific protein mS38 is preferentially required for synthesis of cytochrome c oxidase subunits

Abstract

Message-specific translational regulation mechanisms shape the biogenesis of multimeric oxidative phosphorylation (OXPHOS) enzyme in mitochondria from the yeast Saccharomyces cerevisiae . These mechanisms, driven mainly by the action of mRNA-specific translational activators, help to coordinate synthesis of OXPHOS catalytic subunits by the mitoribosomes with both the import of their nucleus-encoded partners and their assembly to form the holocomplexes. However, little is known regarding the role that the mitoribosome itself may play in mRNA-specific translational regulation. Here, we show that the mitoribosome small subunit protein Cox24/mS38, known to be necessary for mitoribosome-specific intersubunit bridge formation and 15S rRNA H44 stabilization, is required for efficient mitoribogenesis. Consequently, mS38 is necessary to sustain the overall mitochondrial protein synthesis rate, despite an adaptive ∼2-fold increase in mitoribosome abundance in mS38 -deleted cells. Additionally, the absence of mS38 preferentially disturbs translation initiation of COX1, COX2 , and COX3 mRNAs, without affecting the levels of mRNA-specific translational activators. We propose that mS38 confers the mitochondrial ribosome an intrinsic capacity of translational regulation, probably acquired during evolution from bacterial ribosomes to facilitate the translation of mitochondrial mRNAs, which lack typical anti-Shine-Dalgarno sequences.

Cryo-EM study of an archaeal 30S initiation complex gives insights into evolution of translation initiation

“…bS22 conserved in actinobacteria located at the eL41 binding site 71 . Finally, in human and yeast mitochondria, the N-terminal part of the mitochondria-specific mS38 protein occupies this position [72][73][74] . mS38 is proposed to be related to translation of mitochondrial mRNAs lacking typical SD sequences 74 .…”

“…Finally, in human and yeast mitochondria, the N-terminal part of the mitochondria-specific mS38 protein occupies this position [72][73][74] . mS38 is proposed to be related to translation of mitochondrial mRNAs lacking typical SD sequences 74 . Overall, the whole data indicate that variability of eL41 might be related to evolution of translation initiation.…”

An Update on Mitochondrial Ribosome Biology: The Plant Mitoribosome in the Spotlight

“…Specifically, Arabidopsis mitoribosomes altered due to the silencing of the nuclear RPS10 gene encoding mitochondrial ribosomal protein S10 differentially translate two subsets of mRNAs, those encoding OXPHOS subunits and ribosomal proteins with, respectively, slightly lowered and clearly enhanced efficiency compared to the wild-type. A mitoribosome-mediated translation regulation has also been reported for yeast mitoribosome lacking the SSU protein mS38/Cox24 [51]. It was reported that mS38 is preferentially required for translation initiation of COX1, COX2 and COX3 mRNAs.…”

Epitranscriptomics of Mammalian Mitochondrial Ribosomal RNA

“…mS38 protein, which is lacking in E. coli , although present (as an orthologous bS22) in some bacteria which have many leaderless mRNAs, is involved in formation of the channel accommodating mRNA part 5′ to the P-site. In yeast mitochondria this protein was demonstrated to selectively enhance translation of specific mitochondrial mRNAs [ 37 ]. A protein mS37, which is also uniquely found in mitoribosomes also contributes to the accommodation of mRNA 5′-region [ 38 ].…”

“…The protein mS39 binds the small subunit from the cytoplasmic side and facilitate a recruitment of mRNAs [ 39 , 40 ]. Proteins mS37 and mS38 are located in the platform region of the small subunit [ 96 ] and also contribute to the interaction with mRNAs [ 37 , 38 ]. The latter protein is nearest to the modification site.…”