How RNases Shape Mitochondrial Transcriptomes

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(11), P. 6141 - 6141

Published: May 30, 2022

Mitochondria are the power houses of eukaryote cells. These endosymbiotic organelles prokaryote origin considered as semi-autonomous since they have retained a genome and fully functional gene expression mechanisms. pathways particularly interesting because combine features inherited from bacterial ancestor mitochondria with characteristics that appeared during evolution. RNA biology is thus diverse in mitochondria. It involves an unexpectedly vast array factors, some which being universal to all others specific clades. Among them, ribonucleases prominent. They play pivotal functions such maturation transcript ends, degradation surveillance required attain pool mature RNAs synthesize essential mitochondrial proteins respiratory chain proteins. Beyond these functions, also involved maintenance replication DNA, even possibly biogenesis ribosomes. The diversity RNases reviewed here, showing for instance how cases bacterial-type enzyme was kept eukaryotes, while other clades, enzymes were recruited same function.

Language: Английский

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RNA degradation in human mitochondria: the journey is not finished

Human Molecular Genetics, Journal Year: 2024, Volume and Issue: 33(R1), P. R26 - R33

Published: May 22, 2024

Mitochondria are vital organelles present in almost all eukaryotic cells. Although most of the mitochondrial proteins nuclear-encoded, mitochondria contain their own genome, whose proper expression is necessary for function. Transcription human genome results synthesis long polycistronic transcripts that subsequently processed by endonucleases to release individual RNA molecules, including precursors sense protein-encoding mRNA (mt-mRNA) and a vast amount antisense noncoding RNAs. Because DNA (mtDNA) organization, regulation gene at transcriptional level limited. transcription protein-coding genes occurs with same frequency, steady-state levels mature different. Therefore, post-transcriptional processes important regulating mt-mRNA levels. The degradosome complex composed helicase SUV3 (also known as SUPV3L1) polynucleotide phosphorylase (PNPase, PNPT1). It best-characterized RNA-degrading machinery mitochondria, which primarily responsible decay RNA. mechanism less understood. This review aims provide general picture expression, particular focus on (mtRNA) degradation.

Language: Английский

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FASTKD5 processes mitochondrial pre-mRNAs at non-canonical cleavage sites

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 18, 2024

Abstract The regulation of mammalian mitochondrial gene expression is largely post-transcriptional and the first step in translating 13 polypeptides encoded mtDNA endonucleolytic cleavage primary polycistronic transcripts. As rRNAs most mRNAs are flanked by tRNAs, release mature RNAs occurs mostly excision tRNAs. Processing non-canonical mRNAs, not requires FASTKD5, but molecular mechanism remains unknown. To investigate this, we created characterized a knockout cell line to use as an assay system. absence FASTKD5 resulted severe combined OXPHOS assembly defect due inability translate with unprocessed 5’-UTRs. Analysis RNA processing variants allowed us map amino acid residues essential for function. Remarkably, this was substrate-specific, arguing against one size fits all model. A reconstituted vitro system purified protein synthetic substrates showed that on its own able cleave client correctly, non-specific sequences. These results establish missing piece biochemical machinery required completely process transcript.

Language: Английский

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The Vsr-like protein FASTKD4 regulates the stability and polyadenylation of the MT-ND3 mRNA

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

Abstract Expression of the compact mitochondrial genome is regulated by nuclear encoded, mitochondrially localized RNA-binding proteins (RBPs). RBPs regulate lifecycles RNAs from transcription to degradation mediating RNA processing, maturation, stability and translation. The Fas-activated serine/threonine kinase (FASTK) family has been shown fine-tune discrete aspects gene expression. Although roles specific targets FASTK have elucidated, molecular mechanisms in metabolism remain unclear. Therefore, we resolved structure FASTKD4 at atomic level that includes RAP domain two FAST motifs, creating a positively charged cavity resembling very short patch repair endonuclease. Our biochemical studies show binds canonical poly(A) tail MT-ND3 enabling its maturation vitro role consistent with loss cells results decreased polyadenylation, which destabilizes this messenger mitochondria.

Language: Английский

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The human mitochondrial mRNA structurome reveals mechanisms of gene expression

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 2, 2023

Summary The mammalian mitochondrial genome encodes thirteen oxidative phosphorylation system proteins, 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 gene expression unknown. To address this gap, we developed a mitoDMS-MaPseq approach used DREEM clustering to resolve the human mt-mRNA structurome. We gained insights into biology translation regulatory mechanisms, including unique programmed ribosomal frameshifting for ATP8/ATP6 transcript. Furthermore, absence maintenance factor LRPPRC led transcriptome structured differently, with specific mRNA regions exhibiting increased or decreased structuredness. This highlights role maintaining folding promote stabilization efficient translation. In conclusion, our maps reveal novel serving as detailed reference tool studying them different physiological pathological contexts.

Language: Английский

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