Year: 2017
Type: article
Abstract: Adenosine-to-inosine RNA editing in transcripts encoding the voltage-gated potassium channel Kv1.1 converts an isoleucine to valine codon for amino acid 400, speeding channel recovery from inactivation. Numerous Kv1.1 mutations have been associated with the human disorder Episodic Ataxia Type-1 (EA1), characterized by stress-induced ataxia, myokymia, and increased prevalence of seizures. Three EA1 mutations, V404I, I407M, and V408A, are located within the RNA duplex structure required for RNA editing. Each mutation decreased RNA editing both in vitro and using an in vivo mouse model bearing the V408A allele. Editing of transcripts encoding mutant channels affects numerous biophysical properties including channel opening, closing, and inactivation. Thus EA1 symptoms could be influenced not only by the direct effects of the mutations on channel properties, but also by their influence on RNA editing. These studies provide the first evidence that mutations associated with human genetic disorders can affect cis-regulatory elements to alter RNA editing.
Source: Scientific Reports
DOI: 10.1038/srep41095
Language: English
Topic: RNA regulation and disease
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: National Science Foundation, Cystic Fibrosis Foundation, Cystic Fibrosis Foundation Therapeutics, Vanderbilt University, National Institute of Mental Health, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute on Minority Health and Health Disparities, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1584286416, MRI: Acquisition of a Shared Laser Scanning Confocal Microscope at the Institute of Neurobiology, Regulation of the Na/K Pump by RNA Editing, MRI: Procurement of a Shared Confocal Microscope Facility at the Institute of Neurobiology, COBRE Phase 2: Center for Neuroplasticity at the University of Puerto Rico, Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at Vanderbilt University, Site-directed RNA editing: a new method to correct disease causing mutations, Center for Collaborative Research in Health Disparities, Physiological roles of Kv1.1 RNA editing, Multidisciplinary Training in Molecular Endocrinology
OpenAlex ID: W2589208974