Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 43, Pages 11024-11029Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1807258115
Keywords
genome instability; mitochondrial degradosome; R loops; RNA metabolism; transcription-replication conflicts
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Funding
- European Research Council [ERC2014 AdG669898]
- Spanish Ministry of Economy and Competitiveness [BFU2013-42918-P, BFU2016-75058-P]
- European Union (Fondo Europeo de Desarrollo Regional)
- Spanish Ministry of Economy, Industry, and Competitiveness
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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 mitochondria! 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 mitochondria! RNA surveillance and degradation. Here we describe a new role for the mitochondria! degradosome in preventing the accumulation of pathological R loops in the mitochondria! 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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