Tat stimulates cotranscriptional capping of HIV mRNA
Tat stimulates cotranscriptional capping of HIV mRNA
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DOI：
10.1016/s1097-2765(02)00630-5
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发表时间：
2002-09-01
期刊：
影响因子：
16
通讯作者：
Rana, TM
中科院分区：
文献类型：
--
作者：
Chiu, YL;Ho, CK;Rana, TM
在这里，我们研究了HIV前体mRNA的加帽和甲基化如何与Pol II延伸相结合。帽酶（Mce 1）和帽甲基转移酶（Hcm 1）与模板接合的Pol II的稳定结合依赖于CTD磷酸化，但不依赖于新生RNA。在伸长过程中，Mce 1和Hcm 1都与Pol II一起行进。加帽和甲基化反应不能发生，直到新生的前mRNA已经达到19-22个核苷酸的链长。当延伸复合物在启动子近端位置停止时，HIV前mRNA定量地被加帽，但在不受阻碍的Pol II延伸期间加帽效率低得多。达特强烈刺激HIV mRNA的共转录加帽，这种刺激需要达特的C-末端片段介导其与Mce 1的直接结合。我们的研究结果暗示了对HIV基因表达至关重要的延长检查点的加帽。
Here we investigated how capping and methylation of HIV pre-mRNAs are coupled to Pol II elongation. Stable binding of the capping enzyme (Mce1) and cap methyltransferase (Hcm1) to template-engaged Pol II depends on CTD phosphorylation, but not on nascent RNA. Both Mce1 and Hcm1 travel with Pol II during elongation. The capping and methylation reactions cannot occur until the nascent pre-mRNA has attained a chain length of 19-22 nucleotides. HIV pre-mRNAs are capped quantitatively when elongation complexes are halted at promoter-proximal positions, but capping is much less efficient during unimpeded Pol II elongation. Cotranscriptional capping of HIV mRNA is strongly stimulated by Tat, and this stimulation requires the C-terminal segment of Tat that mediates its direct binding to Mce1. Our findings implicate capping in an elongation checkpoint critical to HIV gene expression.