Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function

<p>Abstract</p> <p>Background</p> <p>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...

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Main Authors: Myers Michael P, Kleva Danijela, Knezevich Anna, Guerra Jessica, Kula Anna, Marcello Alessandro
Format: Article
Language:English
Published: BMC 2011-07-01
Series:Retrovirology
Online Access:http://www.retrovirology.com/content/8/1/60
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author Myers Michael P
Kleva Danijela
Knezevich Anna
Guerra Jessica
Kula Anna
Marcello Alessandro
author_facet Myers Michael P
Kleva Danijela
Knezevich Anna
Guerra Jessica
Kula Anna
Marcello Alessandro
author_sort Myers Michael P
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>
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spelling doaj.art-3b1614b74aa64b689c5c9cee1e8edc762022-12-22T02:49:32ZengBMCRetrovirology1742-46902011-07-01816010.1186/1742-4690-8-60Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev functionMyers Michael PKleva DanijelaKnezevich AnnaGuerra JessicaKula AnnaMarcello Alessandro<p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>http://www.retrovirology.com/content/8/1/60
spellingShingle Myers Michael P
Kleva Danijela
Knezevich Anna
Guerra Jessica
Kula Anna
Marcello Alessandro
Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function
Retrovirology
title Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function
title_full Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function
title_fullStr Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function
title_full_unstemmed Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function
title_short Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function
title_sort characterization of the hiv 1 rna associated proteome identifies matrin 3 as a nuclear cofactor of rev function
url http://www.retrovirology.com/content/8/1/60
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