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Inhibition of SNAP25 expression by HIV‐1 Tat involves the activity of mir‐128a
Author(s) -
Eletto Davide,
Russo Giuseppe,
Passiatore Giovanni,
Del Valle Luis,
Giordano Antonio,
Khalili Kamel,
Gualco Elisa,
Peruzzi Francesca
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21452
Subject(s) - microrna , biology , snap25 , microbiology and biotechnology , downregulation and upregulation , messenger rna , translation (biology) , function (biology) , gene expression , gene , genetics , synaptic vesicle , vesicle , membrane
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. J. Cell. Physiol. 216: 764–770, 2008, © 2008 Wiley‐Liss, Inc.