A HERPESVIRUS REGULATORY PROTEIN APPEARS TO ACT POSTTRANSCRIPTIONALLY BY AFFECTING MESSENGER-RNA PROCESSING
A HERPESVIRUS REGULATORY PROTEIN APPEARS TO ACT POSTTRANSCRIPTIONALLY BY AFFECTING MESSENGER-RNA PROCESSING
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DOI：
10.1101/gad.6.5.848
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发表时间：
1992-05-01
影响因子：
10.5
通讯作者：
MENDOZA, GE
中科院分区：
文献类型：
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作者：
SANDRIGOLDIN, RM;MENDOZA, GE
转录后调控机制在许多病毒的基因表达调控中发挥着重要作用，尤其是对晚期基因产物的调控。在这项研究中，我们研究了ICP27的作用方式，ICP27是单纯疱疹病毒1型(HSV-1)晚期基因表达所需的即刻-早期调节蛋白。转染实验表明，ICP27可以根据目的基因的不同激活或抑制表达。在这里，我们证明了ICP27的调节活性不依赖于目标基因启动子序列，而是依赖于不同的mRNA处理信号的存在。激活功能与不同的聚腺苷酸化位点相关，而抑制功能与靶基因编码序列的5‘或3’内含子的存在相关。在通常距离内只有AATAAA识别信号但没有G/U盒的目的基因的转染中，ICP27提高了Poly(A)+RNA的水平。相反，在ICP27存在的情况下，用含有5‘或3’内含子的靶基因转染靶基因，剪接的靶mRNAs减少了5-10倍。这些结果表明，这种基本的HSV-1调节蛋白在转录后影响mRNA的处理，并指出剪接和多聚腺苷化因子之间可能的相互作用。
Post-transcriptional control mechanisms play an important role in regulating gene expression for a number of viruses, especially in the regulation of late gene products. In this study we have investigated the mode of action of ICP27, an immediate-early regulatory protein of herpes simplex virus 1 (HSV-1) required for late gene expression. Transfection experiments have demonstrated that ICP27 can activate or repress expression depending on the target gene. Here, we show that the regulatory activity of ICP27 is independent of the target gene promoter sequences but, instead, depends on the presence of different mRNA processing signals. The activation function correlated with different polyadenylation sites, whereas the repressor function correlated with the presence of introns either 5' or 3' to the target gene-coding sequences. Poly(A)+ RNA levels were increased by ICP27 in transfections with a target gene having only an AATAAA recognition signal but no G/U box within the usual distance. In contrast, in the presence of ICP27, spliced target mRNAs were decreased 5- to 10-fold in transfections with target genes containing a 5' or 3' intron. These results suggest that this essential HSV-1 regulatory protein acts post-transcriptionally to affect mRNA processing and point to possible interactions between splicing and polyadenylation factors.