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

Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):11024-11029. doi: 10.1073/pnas.1807258115. Epub 2018 Oct 9.


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.

Keywords: R loops; RNA metabolism; genome instability; mitochondrial degradosome; transcription–replication conflicts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DEAD-box RNA Helicases / metabolism
  • DNA, Mitochondrial / genetics
  • DNA, Single-Stranded / genetics
  • Endoribonucleases / genetics*
  • Exosome Multienzyme Ribonuclease Complex / metabolism
  • Genome, Mitochondrial / genetics*
  • Genomic Instability / genetics*
  • HeLa Cells
  • Humans
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Multienzyme Complexes / genetics*
  • Polyribonucleotide Nucleotidyltransferase / genetics*
  • RNA Helicases / genetics*
  • RNA Stability / genetics
  • RNA, Double-Stranded / genetics
  • Ribonucleases / metabolism


  • DNA, Mitochondrial
  • DNA, Single-Stranded
  • Multienzyme Complexes
  • RNA, Double-Stranded
  • degradosome
  • Polyribonucleotide Nucleotidyltransferase
  • Endoribonucleases
  • Exosome Multienzyme Ribonuclease Complex
  • Ribonucleases
  • DEAD-box RNA Helicases
  • RNA Helicases