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

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 insta...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2018-10, Vol.115 (43), p.11024-11029
Main Authors: Silva, Sonia, Camino, Lola P., Aguilera, Andrés
Format: Article
Language:English
Subjects:
Accumulation
Biodegradation
Biological Sciences
Cell Line, Tumor
DEAD-box RNA Helicases - metabolism
Degradation
Deoxyribonucleic acid
DNA
DNA helicase
DNA, Mitochondrial - genetics
DNA, Single-Stranded - genetics
Double-stranded RNA
Endoribonucleases - genetics
Exosome Multienzyme Ribonuclease Complex - metabolism
Genome, Mitochondrial - genetics
Genomes
Genomic instability
Genomic Instability - genetics
HeLa Cells
Humans
Metabolism
Mitochondria
Mitochondria - genetics
Mitochondria - metabolism
Mitochondrial DNA
Molecular modelling
Multienzyme Complexes - genetics
Polynucleotide phosphorylase
Polyribonucleotide Nucleotidyltransferase - genetics
Ribonucleases - metabolism
Ribonucleic acid
RNA
RNA helicase
RNA Helicases - genetics
RNA Stability - genetics
RNA, Double-Stranded - genetics
Single-stranded DNA
Surveillance
Transcription
Transcription factors
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1807258115