Journal
NUCLEUS
Volume 6, Issue 1, Pages 23-29Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/19491034.2015.1004952
Keywords
Amyotrophic lateral sclerosis (ALS); RNA-DNA hybrid; R-loop; genome instability; stress granules; C9ORF72; SOD1; Senataxin; Ataxin2; TDP43; FUS
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Funding
- Vanier Doctoral Award from the Canadian Institutes of Health Research (CIHR)
- Open Operating Grant from the Canadian Institutes of Health Research (CIHR)
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Amyotrophic lateral sclerosis (ALS) is a severely debilitating neurodegenerative disease linked to mutations in various genes implicated in cytoplasmic RNA metabolism. Recent studies from genetic models have also helped reveal connections between various ALS-linked factors and RNA-DNA hybrid (R-loop) regulation. Here, we examine how such hybrid-regulatory processes are pointing to a key role for the nucleus in ALS. We also present a potential molecular mechanism in which hybrids may represent at least one of the long sought after missing links between different ALS genes. Our opinion is that RNA-DNA hybrids will play a key role in deciphering ALS and other human diseases.
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