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The human mitochondrial mRNA structurome reveals mechanisms of gene expression

ABSTRACT: The mammalian mitochondrial genome encodes thirteen proteins of the oxidative phosphorylation system, crucial in aerobic energy transduction. These proteins are translated from 9 monocistronic and 2 bicistronic transcripts, whose native structures remain unexplored, leaving fundamental molecular determinants of mitochondrial gene expression unknown. To address this knowledge gap, we developed a mitoDMS-MaPseq approach and used DREEM clustering to resolve the native mt-mRNA structurome in human mitochondria. In this way, we gained insights into mt-mRNA biology and translation regulatory mechanisms, including a unique translational frameshifting for the ATP8/ATP6 transcript. Furthermore, absence of the mt-mRNA maintenance factor LRPPRC led to a mitochondrial transcriptome structured differently, with specific mRNA regions exhibiting increased or decreased structuredness. This highlights the role of LRPPRC in maintaining mRNA folding to promote mt-mRNA stabilization and efficient translation. In conclusion, our mt-mRNA folding maps reveal novel mitochondrial gene expression mechanisms, serving as a detailed reference and tool for studying them in different physiological and pathological contexts.

ORGANISM(S): Homo sapiens

PROVIDER: GSE246523 | GEO | 2024/07/19

REPOSITORIES: GEO

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