An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export.
An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export.
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DOI：
10.1371/journal.ppat.1002138
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发表时间：
2011-07
期刊：
影响因子：
6.7
通讯作者：
Whitehouse A
中科院分区：
文献类型：
--
作者：
Jackson BR;Boyne JR;Noerenberg M;Taylor A;Hautbergue GM;Walsh MJ;Wheat R;Blackbourn DJ;Wilson SA;Whitehouse A
hTREX 复合物通过与输出接头 Aly 直接相互作用招募核输出因子 TAP，介导细胞大量 mRNA 核输出。然而有趣的是，Aly 的消耗仅导致细胞 mRNA 核输出的适度减少，这表明存在额外的 mRNA 核输出接头蛋白。为了有效地从细胞核输出卡波西肉瘤相关疱疹病毒 (KSHV) 无内含子 mRNA，KSHV ORF57 蛋白将 hTREX 招募到病毒无内含子 mRNA 上，从而允许进入 TAP 介导的输出途径。然而，类似地，Aly 的耗尽仅导致 KSHV 无内含子 mRNA 的核输出适度减少。在此，我们发现了 ORF57 和细胞蛋白 UIF 之间的一种新的相互作用。我们提供了第一个证据，证明 ORF57-UIF 相互作用能够在 Aly 耗尽的细胞中将 hTREX 和 TAP 招募到 KSHV 无内含子 mRNA 中。引人注目的是，Aly 和 UIF 的消耗会抑制 ORF57 介导的核输出能力核糖核蛋白颗粒的形成，从而阻止 ORF57 介导的 mRNA 核输出和 KSHV 蛋白的产生。重要的是，这些发现强调真核系统中涉及无内含子 KSHV mRNA 的 mRNA 核输出的某些 hTREX 组件存在冗余。疱疹病毒劫持细胞成分以增强病毒基因表达。这对于疱疹病毒无内含子 mRNA 的有效核输出以允许病毒蛋白的产生尤其重要。我们之前已经证明，卡波西肉瘤相关疱疹病毒编码一种保守蛋白 ORF57，该蛋白将必需的细胞 mRNA 输出蛋白招募到病毒无内含子 mRNA 上，形成具有输出能力的病毒核糖核蛋白颗粒。具体来说，我们已经证明 ORF57 直接与细胞输出接头蛋白 Aly 相互作用，以招募其他细胞 mRNA 输出蛋白。然而，令人惊讶的是，Aly 的消耗对细胞和病毒 mRNA 核输出水平的影响有限，表明输出途径存在一定程度的冗余以及其他输出接头蛋白的存在。在这里，我们发现了 ORF57 和第二种输出接头蛋白 UIF 之间的新型相互作用。我们首次证明，在缺乏 Aly 的细胞中，ORF57-UIF 相互作用允许将必需的细胞 mRNA 输出蛋白招募到病毒无内含子 mRNA 上。然而，Aly 和 UIF 的耗尽阻止了具有输出能力的病毒核糖核蛋白颗粒的形成，这表明 Aly 或 UIF 必须存在才能实现有效的 KSHV 无内含子 mRNA 核输出和蛋白质生产。
The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway. Similarly however, depletion of Aly only leads to a modest reduction in the nuclear export of KSHV intronless mRNAs. Herein, we identify a novel interaction between ORF57 and the cellular protein, UIF. We provide the first evidence that the ORF57-UIF interaction enables the recruitment of hTREX and TAP to KSHV intronless mRNAs in Aly-depleted cells. Strikingly, depletion of both Aly and UIF inhibits the formation of an ORF57-mediated nuclear export competent ribonucleoprotein particle and consequently prevents ORF57-mediated mRNA nuclear export and KSHV protein production. Importantly, these findings highlight that redundancy exists in the eukaryotic system for certain hTREX components involved in the mRNA nuclear export of intronless KSHV mRNAs. Herpesviruses hijack cellular components to enhance viral gene expression. This is particularly important for the efficient nuclear export of herpesvirus intronless mRNAs to allow the production of viral proteins. We have previously demonstrated that Kaposi's sarcoma-associated herpesvirus encodes a conserved protein, ORF57, which recruits essential cellular mRNA export proteins onto the viral intronless mRNAs to form an export competent viral ribonucleoprotein particle. Specifically, we have shown that ORF57 interacts directly with the cellular export adaptor protein, Aly, to recruit other cellular mRNA export proteins. Surprisingly however, depletion of Aly has a limited effect on both cellular and viral mRNA nuclear export levels, suggesting a degree of redundancy in the export pathways and the existence of other export adaptor proteins. Here we have identified a novel interaction between ORF57 and a second export adaptor protein, UIF. We show for the first time that the ORF57-UIF interaction allows the recruitment of the essential cellular mRNA export proteins onto viral intronless mRNA, in cells lacking Aly. However, depletion of both Aly and UIF prevents the formation of an export competent viral ribonucleoprotein particle, suggesting that either Aly or UIF must be present for efficient KSHV intronless mRNA nuclear export and protein production.
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