Emerging role of rna-dna hybrids in c9orf72-linked neurodegeneration

Jiou Wang, Aaron R. Haeusler, Eric Aj Simko

Research output: Contribution to journalArticle

Abstract

RNA plays an active role in structural polymorphism of the genome through the formation of stable RNA-DNA hybrids (R-loops). R-loops can modulate normal physiological processes and are also associated with pathological conditions, such as those related to nucleotide repeat expansions. A guanine-rich hexanucleotide repeat expansion in chromosome 9 open reading frame 72 ( C9orf72) has been linked to a spectrum of neurological conditions including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we discuss the possible roles, both locally and genome-wide, of R-loops that may arise from the C9orf72 hexanucleotide repeat. R-loops have the potential to infl uence the pathological processes identified in many repeat expansion diseases, such as repeat instability, transcriptional dysregulation, epigenetic modification, and antisense-mediated gene regulation. We propose that, given the wide-ranging consequences of R-loops in the cell, these structures could underlie multiple pathological processes in C9orf72-linked neurodegeneration.

Original languageEnglish (US)
Pages (from-to)526-532
Number of pages7
JournalCell cycle (Georgetown, Tex.)
Volume14
Issue number4
DOIs
StatePublished - Feb 15 2015

Fingerprint

Chromosomes, Human, Pair 9
Open Reading Frames
RNA
Pathologic Processes
Genome
Physiological Phenomena
Guanine
Epigenomics
Nucleotides
DNA
Genes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Emerging role of rna-dna hybrids in c9orf72-linked neurodegeneration. / Wang, Jiou; Haeusler, Aaron R.; Simko, Eric Aj.

In: Cell cycle (Georgetown, Tex.), Vol. 14, No. 4, 15.02.2015, p. 526-532.

Research output: Contribution to journalArticle

Wang, Jiou ; Haeusler, Aaron R. ; Simko, Eric Aj. / Emerging role of rna-dna hybrids in c9orf72-linked neurodegeneration. In: Cell cycle (Georgetown, Tex.). 2015 ; Vol. 14, No. 4. pp. 526-532.
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