Altered subcellular localization of the NeuN/Rbfox3 RNA splicing factor in HIV-associated neurocognitive disorders (HAND).
The anti-NeuN antibody has been widely used for over 15 years to unambiguously identify post-mitotic neurons in the central nervous system of a wide variety of vertebrates including mice, rats and humans. In contrast to its widely reported nuclear localization, we found significantly higher NeuN reactivity in the cytoplasm of neurons in brain sections from HIV-infected individuals with cognitive impairment compared to controls. The protein target of anti-NeuN antisera was recently identified as the neuron-specific RNA splicing factor, Rbfox3, but its significance in diseases affecting the brain has not been previously reported. RNA splicing occurs in the nucleus hence, the altered localization of RbFox3 to the cytoplasm may lead to the downregulation of neuronal gene expression.
Johns Hopkins University School of Medicine, Department of Neurology, 600 North Wolfe Street, Meyer 6-181, Baltimore, MD 21287, USA. Electronic address: clucas7@jhu.edu.
Calixto-Hope
CH
Lucas
Johns Hopkins University School of Medicine, Department of Neurology, 600 North Wolfe Street, Meyer 6-181, Baltimore, MD 21287, USA. Electronic address: Mathilde.calvez@ens-lyon.fr.
Mathilde
M
Calvez
Johns Hopkins University School of Medicine, Department of Neurology, 600 North Wolfe Street, Meyer 6-181, Baltimore, MD 21287, USA. Electronic address: robabu@gmail.com.
Roshni
R
Babu
Johns Hopkins University School of Medicine, Department of Neurology, 600 North Wolfe Street, Meyer 6-181, Baltimore, MD 21287, USA. Electronic address: abrown76@jhmi.edu.
Amanda
A
Brown
D015526:AIDS Dementia Complex / Q000378:metabolism*; D000328:Adult; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism; D003072:Cognition Disorders / Q000378:metabolism* / Q000821:virology; D018792:Encephalitis, Viral / Q000378:metabolism* / Q000821:virology; D005260:Female; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D012326:RNA Splicing
D034961:Antigens, Nuclear; D009419:Nerve Tissue Proteins; C506808:neuronal nuclear antigen NeuN, human
Gene expression; HIV-associated neurocognitive disorders; NeuN; Neurodegeneration; Rbfox3; Splicing