title: Inhibition of SNAP25 expression by HIV-1 Tat involves the activity of mir-128a.
abstract: MicroRNAs (miRs) are short endogenous RNAs that regulate gene expression by incomplete pairing with messenger RNAs. An increasing number of studies show that mammalian microRNAs play fundamental roles in various aspects of cellular function including differentiation, proliferation, and cell death. Recent findings demonstrating the presence of microRNAs in mature neuronal dendrites suggest their possible involvement in controlling local protein translation and synaptic function. HIV-1 Encephalopathy (HIVE) is a manifestation of HIV-1 infection that often results in neuronal damage and dysfunction. While neurons are rarely, if ever, infected by HIV-1, they are exposed to cytotoxic viral and cellular factors including the HIV-1 transactivating factor Tat. In this study, we show that Tat deregulates expression levels of selected microRNAs, including the neuronal mir-128, in primary cortical neurons. We further show that mir-128a inhibits expression of the pre-synaptic protein SNAP25, whereas the anti-mir-128a partially restores Tat/mir-128a-induced downregulation of SNAP25 expression. Altogether, our data provide a novel mechanism by which HIV-Tat perturbs neuronal activity.
authors.affiliation: Department of Neuroscience and Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19112, USA.
authors.forename: Davide
authors.initials: D
authors.lastname: Eletto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Russo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Passiatore
authors.forename: Luis
authors.initials: L
authors.lastname: Del Valle
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.forename: Elisa
authors.initials: E
authors.lastname: Gualco
authors.forename: Francesca
authors.initials: F
authors.lastname: Peruzzi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D015203:Reproducibility of Results; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D050825:Synaptosomal-Associated Protein 25; D054322:tat Gene Products, Human Immunodeficiency Virus