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Báo cáo y học: "Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function. | Kula et al. Retrovirology 2011 8 60 http www.retrovirology.eom content 8 1 60 RETR0VIR0L0GY RESEARCH Open Access Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function 1 13 11 2 1 Anna Kula Jessica Guerra Anna Knezevich Danijela Kleva Michael P Myers and Alessandro Marcello Abstract Background Central to the fully competent replication cycle of the human immunodeficiency virus type 1 HIV-1 is the nuclear export of unspliced and partially spliced RNAs mediated by the Rev posttranscriptional activator and the Rev response element RRE . Results Here we introduce a novel method to explore the proteome associated with the nuclear HIV-1 RNAs. At the core of the method is the generation of cell lines harboring an integrated provirus carrying RNA binding sites for the MS2 bacteriophage protein. Flag-tagged MS2 is then used for affinity purification of the viral RNA. By this approach we found that the viral RNA is associated with the host nuclear matrix component MATR3 Matrin 3 and that its modulation affected Rev activity. Knockdown of MATR3 suppressed Rev RRE function in the export of unspliced HIV-1 RNAs. However MATR3 was able to associate with Rev only through the presence of RRE-containing viral RNA. Conclusions In this work we exploited a novel proteomic method to identify MATR3 as a cellular cofactor of Rev activity. MATR3 binds viral RNA and is required for the Rev RRE mediated nuclear export of unspliced HIV-1 RNAs. Introduction Viruses have evolved to optimize their replication potential in the host cell. For this purpose viruses take advantage of the molecular strategies of the infected host and therefore represent invaluable tools to identify novel cellular mechanisms that modulate gene expression 1 . The primary viral transcription product is utilized in unspliced and alternatively spliced forms to direct the synthesis of all human immunodeficiency virus HIV-1 proteins. Although nuclear export of .