R-Loops in Motor Neuron Diseases

Martina G.L. Perego, Michela Taiana, Nereo Bresolin, Giacomo P. Comi, Stefania Corti

Research output: Contribution to journalArticlepeer-review

Abstract

R loops are transient three-stranded nucleic acid structures that form physiologically during transcription when a nascent RNA transcript hybridizes with the DNA template strand, leaving a single strand of displaced nontemplate DNA. However, aberrant persistence of R-loops can cause DNA damage by inducing genomic instability. Indeed, evidence has emerged that R-loops might represent a key element in the pathogenesis of human diseases, including cancer, neurodegeneration, and motor neuron disorders. Mutations in genes directly involved in R-loop biology, such as SETX (senataxin), or unstable DNA expansion eliciting R-loop generation, such as C9ORF72 HRE, can cause DNA damage and ultimately result in motor neuron cell death. In this review, we discuss current advancements in this field with a specific focus on motor neuron diseases associated with deregulation of R-loop structures. These mechanisms can represent novel therapeutic targets for these devastating, incurable diseases.

Original languageEnglish
Pages (from-to)2579-2589
JournalMolecular Neurobiology
Volume56
Issue number4
DOIs
Publication statusPublished - 2019

Keywords

  • Amyotrophic lateral sclerosis
  • DNA damage
  • Motor neuron disease
  • R-loops
  • Spinal muscular atrophy

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

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