C9orf72 Disease-Related Foci Are Each Composed of One Mutant Expanded Repeat RNA.

ABSTRACT: The chromosome 9 open reading frame 72 (c9orf72) gene contains a hexanucleotide (GGGGCC) repeat expansion responsible for many cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The mutant intronic RNA forms "foci" within nuclei, but the connection between transcript expression, foci, and biochemical disease mechanisms is unclear. Knowing the absolute numbers of cellular RNAs, in any system, is important for understanding the molecular mechanisms of natural physiology, disease, and drug action. Absolute numbers, however, are rarely determined, and this absence is a major impediment to understanding complex systems. Using quantitative methods, we demonstrate that foci are single RNA molecules. Most cells have no foci while 1%-2% have more than ten. Knowing the n

SUBMITTER: Liu J 

PROVIDER: S-EPMC5316317 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature