ADAR2 mislocalization and widespread RNA editing aberrations in C9orf72-mediated ALS/FTD.

ABSTRACT: The hexanucleotide repeat expansion GGGGCC (G₄C₂)_n in the C9orf72 gene is the most common genetic abnormality associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent findings suggest that dysfunction of nuclear-cytoplasmic trafficking could affect the transport of RNA binding proteins in C9orf72 ALS/FTD. Here, we provide evidence that the RNA editing enzyme adenosine deaminase acting on RNA 2 (ADAR2) is mislocalized in C9orf72 repeat expansion mediated ALS/FTD. ADAR2 is responsible for adenosine (A) to inosine (I) editing of double-stranded RNA, and its function has been shown to be essential for survival. Here we show the mislocalization of ADAR2 in human induced pluripotent stem cell-derived motor neurons (hiPSC-MNs)

SUBMITTER: Moore S 

PROVIDER: S-EPMC6750285 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature