Differential effects of hnRNP D/AUF1 isoforms on HIV-1 gene expression.
Differential effects of hnRNP D/AUF1 isoforms on HIV-1 gene expression.
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DOI：
10.1093/nar/gkr1238
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发表时间：
2012-04
影响因子：
14.9
通讯作者：
Cochrane A
中科院分区：
文献类型：
--
作者：
Lund N;Milev MP;Wong R;Sanmuganantham T;Woolaway K;Chabot B;Abou Elela S;Mouland AJ;Cochrane A
RNA加工的控制在HIV-1基因表达中起着重要作用。为了探索几种hnRNP蛋白在这一过程中的作用，我们进行了siRNA筛选，以检查hnRNP A1，A2，D，H，I和K的缺失对HIV-1基因表达的影响。虽然hnRNP H，I或K的损失几乎没有影响，但A1和A2的消耗增加了病毒结构蛋白的表达。相反，hnRNP D表达减少减少HIV-1 Gag和Env的合成。hnRNP D的丢失不会引起病毒RNA丰度的变化，但会减少HIV-1未剪接和单剪接RNA在细胞质中的积累。随后的分析确定hnRNP D在HIV-1感染后重新定位于细胞质，并与Gag蛋白相关。hnRNP D的四种同种型的筛选确定，在过表达时，它们对HIV-1 Gag表达具有不同的作用，p45和p42同种型增加病毒Gag合成，而p40和p37抑制病毒Gag合成。hnRNP D同种型对HIV-1表达的不同作用表明，它们的相对丰度可能有助于细胞类型复制病毒的许可，随后通过p45和p42的选择性耗竭证实了这一假设。
Control of RNA processing plays a major role in HIV-1 gene expression. To explore the role of several hnRNP proteins in this process, we carried out a siRNA screen to examine the effect of depletion of hnRNPs A1, A2, D, H, I and K on HIV-1 gene expression. While loss of hnRNPs H, I or K had little effect, depletion of A1 and A2 increased expression of viral structural proteins. In contrast, reduced hnRNP D expression decreased synthesis of HIV-1 Gag and Env. Loss of hnRNP D induced no changes in viral RNA abundance but reduced the accumulation of HIV-1 unspliced and singly spliced RNAs in the cytoplasm. Subsequent analyses determined that hnRNP D underwent relocalization to the cytoplasm upon HIV-1 infection and was associated with Gag protein. Screening of the four isoforms of hnRNP D determined that, upon overexpression, they had differential effects on HIV-1 Gag expression, p45 and p42 isoforms increased viral Gag synthesis while p40 and p37 suppressed it. The differential effect of hnRNP D isoforms on HIV-1 expression suggests that their relative abundance could contribute to the permissiveness of cell types to replicate the virus, a hypothesis subsequently confirmed by selective depletion of p45 and p42.
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