title: miR-886-3p levels are elevated in Friedreich ataxia.
abstract: Friedreich ataxia (FRDA) is the most common inherited ataxia caused primarily by an intronic GAA.TTC triplet repeat expansion in the frataxin (FXN) gene. FXN RNA and protein levels are reduced in patients leading to progressive gait and limb ataxia, sensory loss, reduced tendon reflexes, dysarthria, absent lower limb reflexes, and loss of position and vibration sense. Neurological manifestations ensue from primary loss of dorsal root ganglia neurons and their associated axons ascending centrally in the spinal cord and peripherally in large myelinated nerves. Small noncoding RNAs such as microRNAs have been shown to be dysregulated in neurodegenerative diseases such as Alzheimer's and Huntington's disease. Here we report that hsa-miR-886-3p (miR-886-3p) was increased in patient cells as well as peripheral patient blood samples. Selective reduction in miR-886-3p by an anti-miR led to elevation of FXN message and protein levels without associated changes in histone marks at the FXN locus. Nevertheless, derepression of frataxin by a histone deacetylase inhibitor leads to a decrease in miR-886-3p. These results outline involvement of a small RNA, miR-886-3p in FRDA and a novel therapeutic approach to this disease using an anti-miR-886-3p.
authors: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10065, USA. lam2022@med.cornell.edu
authors: Lata H
authors: LH
authors: Mahishi
authors: Ronald P
authors: RP
authors: Hart
authors: David R
authors: DR
authors: Lynch
authors: Rajiv R
authors: RR
authors: Ratan
mesh_terms: D002460:Cell Line; D005621:Friedreich Ataxia / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006657:Histones / Q000378:metabolism; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D018911:Trinucleotide Repeats / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*; D000096923:Frataxin
chemical_list: D006657:Histones; D033862:Iron-Binding Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000096923:Frataxin; C544065:AGTR1 protein, human; C559060:MIRN886 microRNA, human