Nuclear matrix protein Matrin 3 is a regulator of ZAP-mediated retroviral restriction.
Nuclear matrix protein Matrin 3 is a regulator of ZAP-mediated retroviral restriction.
复制标题
DOI：
10.1186/s12977-015-0182-4
复制
发表时间：
2015-07-01
期刊：
影响因子：
3.3
通讯作者：
Goff SP
中科院分区：
文献类型：
--
作者：
Erazo A;Goff SP
Matrin 3是一种参与多个核过程的核基质蛋白。在HIV-1感染中，Matrin 3作为Rev辅因子，对HIV-1转录物的细胞质积累很重要。ZAP是多种病毒的有效宿主限制因子，包括逆转录病毒HIV-1和MoMuLV。在这项研究中，我们试图进一步表征Matrin 3在HIV基因表达调控中的功能。在这里，我们描述了一个功能Matrin 3作为负调节ZAP介导的限制逆转录病毒。Matrin 3相关蛋白的质谱分析揭示了与ZAP降解复合物DDX 17和EXOSC 3蛋白的相互作用。免疫共沉淀研究证实了Matrin 3与DDX 17、EXOSC 3和ZAP的关联，在很大程度上依赖于RNA，表明RNA介导了Matrin 3与ZAP降解复合物的这些组分的相互作用。沉默Matrin 3的表达引起了显着增强ZAP驱动的抑制HIV-1和MoMuLV荧光素酶报告病毒。这种效应与额外的核基质蛋白共享。ZAP靶向多重剪接的HIV-1转录物，但在Matrin 3抑制的背景下，这种ZAP限制被扩大到未剪接和多重剪接的RNA。在这里，我们揭示了一个前所未有的作用，核基质蛋白，Matrin 3，在ZAP的抗逆转录病毒活性的调节。抑制Matrin 3增强了对HIV-1基因表达的更高和更广泛的ZAP限制。这项研究表明，这种ZAP的调节机制是共享与其他核基质蛋白。
Matrin 3 is a nuclear matrix protein involved in multiple nuclear processes. In HIV-1 infection, Matrin 3 serves as a Rev cofactor important for the cytoplasmic accumulation of HIV-1 transcripts. ZAP is a potent host restriction factor of multiple viruses including retroviruses HIV-1 and MoMuLV. In this study we sought to further characterize Matrin 3 functions in the regulation of HIV gene expression. Here we describe a function for Matrin 3 as a negative regulator of the ZAP-mediated restriction of retroviruses. Mass spectrometry analysis of Matrin 3-associated proteins uncovered interactions with proteins of the ZAP degradation complex, DDX17 and EXOSC3. Coimmunoprecipitation studies confirmed Matrin 3 associations with DDX17, EXOSC3 and ZAP, in a largely RNA-dependent manner, indicating that RNA is mediating the Matrin 3 interactions with these components of the ZAP degradation complex. Silencing Matrin 3 expression caused a remarkably enhanced ZAP-driven inhibition of HIV-1 and MoMuLV luciferase reporter viruses. This effect was shared with additional nuclear matrix proteins. ZAP targets multiply-spliced HIV-1 transcripts, but in the context of Matrin 3 suppression, this ZAP restriction was broadened to unspliced and multiply-spliced RNAs. Here we reveal an unprecedented role for a nuclear matrix protein, Matrin 3, in the regulation of ZAP’s antiretroviral activity. Suppressing Matrin 3 powers a heightened and broader ZAP restriction of HIV-1 gene expression. This study suggests that this ZAP regulatory mechanism is shared with additional nuclear matrix proteins.
登录
查看更多内容
影响因子：
7.3
作者：
Jarmoskaite, Inga;Russell, Rick
通讯作者：
Russell, Rick
ZAP N 端结构域的结构表明锌指蛋白如何识别复杂的 RNA
影响因子：
16.8
作者：
Chen, Shoudeng;Xu, Yihui;Liu, Yingfang
通讯作者：
Liu, Yingfang
影响因子：
5.4
作者：
Law, Lok Man J.;Albin, Owen R.;MacDonald, Margaret R.
通讯作者：
MacDonald, Margaret R.
影响因子：
25
作者：
Johnson, Janel O.;Pioro, Erik P.;Boehringer, Ashley;Chia, Ruth;Feit, Howard;Renton, Alan E.;Pliner, Hannah A.;Abramzon, Yevgeniya;Marangi, Giuseppe;Winborn, Brett J.;Gibbs, J. Raphael;Nalls, Michael A.;Morgan, Sarah;Shoai, Maryam;Hardy, John;Pittman, Alan;Orrell, Richard W.;Malaspina, Andrea;Sidle, Katie C.;Fratta, Pietro;Harms, Matthew B.;Baloh, Robert H.;Pestronk, Alan;Weihl, Conrad C.;Rogaeva, Ekaterina;Zinman, Lorne;Drory, Vivian E.;Borghero, Giuseppe;Mora, Gabriele;Calvo, Andrea;Rothstein, Jeffrey D.;Drepper, Carsten;Sendtner, Michael;Singleton, Andrew B.;Taylor, J. Paul;Cookson, Mark R.;Restagno, Gabriella;Sabatelli, Mario;Bowser, Robert;Chio, Adriano;Traynor, Bryan J.
通讯作者：
Traynor, Bryan J.
影响因子：
2.5
作者：
JANABI, N;PEUDENIER, S;TARDIEU, M
通讯作者：
TARDIEU, M