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

AuthorsSilva, Sonia; Camino, Lola P.; Aguilera, Andrés
KeywordsGenome instability
Mitochondrial degradosome
R loops
RNA metabolism
Issue Date23-Oct-2018
PublisherNational Academy of Sciences (U.S.)
CitationProceedings of the National Academy of Sciences of the USA 115(43): 11024-11029 (2018)
AbstractR 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.
Publisher version (URL)https://doi.org/10.1073/pnas.1807258115
Appears in Collections:(CABIMER) Artículos
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