Human mitochondrial RNA turnover caught in flagranti: involvement of hSuv3p helicase in RNA surveillance

Abstract The cytochrome b gene in Saccharomyces cerevisiae, COB, is encoded by the mitochondrial genome. Nuclear-encoded Cbp1 protein is required specifically for COB mRNA stabilization. Cbp1 interacts with a CCG element in a 64-nucleotide sequence in the 5′-untranslated region of COB mRNA. Mutation of any nucleotide in the CCG causes the same phenotype as cbp1 mutations, i.e., destabilization of both COB precursor and mature message. In this study, eleven nuclear suppressors of single-nucleotide mutations in CCG were isolated and characterized. One dominant suppressor is in CBP1, while the other 10 semidominant suppressors define five distinct linkage groups. One group of four mutations is in PET127, which is required for 5′ end processing of several mitochondrial mRNAs. Another mutation is linked to DSS1, which is a subunit of mitochondrial 3′ → 5′ exoribonuclease. A mutation linked to the SOC1 gene, previously defined by recessive mutations that suppress cbp1 ts alleles and stabilize many mitochondrial mRNAs, was also isolated. We hypothesize that the products of the two uncharacterized genes also affect mitochondrial RNA turnover.

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High-Throughput Measurement of Mitochondrial RNA Turnover in Human Cultured Cells

Methods in Molecular Biology - Mitochondrial Gene Expression ◽

10.1007/978-1-0716-0834-0_11 ◽

2020 ◽

pp. 133-146

Author(s):

Anna V. Kotrys ◽

Lukasz S. Borowski ◽

Roman J. Szczesny

Keyword(s):

High Throughput ◽

Cultured Cells ◽

Mitochondrial Rna ◽

Rna Turnover

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Regulated and quality-control mRNA turnover pathways in eukaryotes

Biochemical Society Transactions ◽

10.1042/bst0381506 ◽

2010 ◽

Vol 38 (6) ◽

pp. 1506-1510 ◽

Cited By ~ 16

Author(s):

Boris Reznik ◽

Jens Lykke-Andersen

Keyword(s):

Quality Control ◽

Rna Processing ◽

Rna Localization ◽

Rna Degradation ◽

Eukaryotic Cells ◽

Mrna Turnover ◽

Surveillance Systems ◽

Rna Turnover ◽

Rna Surveillance ◽

Multiple Levels

Gene expression can be regulated at multiple levels, including transcription, RNA processing, RNA localization, translation and, finally, RNA turnover. RNA degradation may occur at points along the processing pathway or during translation as it undergoes quality control by RNA surveillance systems. Alternatively, mRNAs may be subject to regulated degradation, often mediated by cis-encoded determinants in the mRNA sequence that, through the recruitment of trans factors, determine the fate of the mRNA. The aim of the present review is to highlight mechanisms of regulated and quality-control RNA degradation in eukaryotic cells, with an emphasis on mammals.

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Balance between Transcription and RNA Degradation Is Vital forSaccharomyces cerevisiaeMitochondria: Reduced Transcription Rescues the Phenotype of Deficient RNA Degradation

Molecular Biology of the Cell ◽

10.1091/mbc.e05-08-0796 ◽

2006 ◽

Vol 17 (3) ◽

pp. 1184-1193 ◽

Cited By ~ 29

Author(s):

Agata T. Rogowska ◽

Olga Puchta ◽

Anna M. Czarnecka ◽

Aneta Kaniak ◽

Piotr P. Stepien ◽

...

Keyword(s):

Mitochondrial Gene ◽

Rna Degradation ◽

Transcription Rate ◽

Mitochondrial Rna ◽

Rna Turnover ◽

Loss Of Function ◽

Mitochondrial Rna Polymerase ◽

Genes Encoding ◽

Mitochondrial Introns ◽

Synthesis And Degradation

The Saccharomyces cerevisiae SUV3 gene encodes the helicase component of the mitochondrial degradosome (mtEXO), the principal 3′-to-5′ exoribonuclease of yeast mitochondria responsible for RNA turnover and surveillance. Inactivation of SUV3 (suv3Δ) causes multiple defects related to overaccumulation of aberrant transcripts and precursors, leading to a disruption of mitochondrial gene expression and loss of respiratory function. We isolated spontaneous suppressors that partially restore mitochondrial function in suv3Δ strains devoid of mitochondrial introns and found that they correspond to partial loss-of-function mutations in genes encoding the two subunits of the mitochondrial RNA polymerase (Rpo41p and Mtf1p) that severely reduce the transcription rate in mitochondria. These results show that reducing the transcription rate rescues defects in RNA turnover and demonstrates directly the vital importance of maintaining the balance between RNA synthesis and degradation.

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Mitochondrial RNA Turnover in Metazoa

RNA Metabolism in Mitochondria - Nucleic Acids and Molecular Biology ◽

10.1007/978-3-319-78190-7_2 ◽

2018 ◽

pp. 17-46

Author(s):

Christoph Freyer ◽

Paula Clemente ◽

Anna Wredenberg

Keyword(s):

Mitochondrial Rna ◽

Rna Turnover

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Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1807258115 ◽

2018 ◽

Vol 115 (43) ◽

pp. 11024-11029 ◽

Cited By ~ 20

Author(s):

Sonia Silva ◽

Lola P. Camino ◽

Andrés Aguilera

Keyword(s):

Mitochondrial Dna ◽

Molecular Mechanisms ◽

Genome Instability ◽

Dna Helicase ◽

Genome Integrity ◽

Mitochondrial Rna ◽

Biological Functions ◽

Rna Surveillance ◽

Nucleic Acid Structures ◽

Rna And Dna

R loops are nucleic acid structures comprising an DNA–RNA hybrid and a displaced single-stranded DNA. These structures may occur transiently during transcription, playing essential biological functions. However, persistent R loops may become pathological as they are important drivers of genome instability and have been associated with human diseases. The mitochondrial degradosome is a functionally conserved complex from bacteria to human mitochondria. It is composed of the ATP-dependent RNA and DNA helicase SUV3 and the PNPase ribonuclease, playing a central role in mitochondrial RNA surveillance and degradation. Here we describe a new role for the mitochondrial degradosome in preventing the accumulation of pathological R loops in the mitochondrial DNA, in addition to preventing dsRNA accumulation. Our data indicate that, similar to the molecular mechanisms acting in the nucleus, RNA surveillance mechanisms in the mitochondria are crucial to maintain its genome integrity by counteracting pathological R-loop accumulation.

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