Limited redundancy in genes regulated by Cyclin T2 and Cyclin T1.
Limited redundancy in genes regulated by Cyclin T2 and Cyclin T1.
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DOI：
10.1186/1756-0500-4-260
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发表时间：
2011-07-26
影响因子：
1.8
通讯作者：
Rice AP
中科院分区：
文献类型：
--
作者：
Ramakrishnan R;Yu W;Rice AP
延伸阶段，像RNA聚合酶II转录的其他步骤一样，受到调控。正转录延伸因子B（P-TEF B）复合物允许mRNA合成过渡到生产性延伸阶段。P-TEFb含有Cdk 9（细胞周期蛋白依赖性激酶9）作为其催化亚基，并受其细胞周期蛋白伴侣细胞周期蛋白T1和细胞周期蛋白T2的调节。HIV-1达特反式激活蛋白通过专门将Cdk 9-细胞周期蛋白T1 P-TEFb复合物募集到新生病毒转录物中称为TAR的RNA元件来增强病毒基因表达。细胞周期蛋白T1和细胞周期蛋白T2在原代单核细胞和CD 4 + T细胞中的表达模式表明，细胞周期蛋白T2通常可能参与静止细胞中组成型表达基因的表达，而细胞周期蛋白T1可能参与在巨噬细胞分化、T细胞活化和代谢活性增加的条件下上调的基因的表达。我们希望鉴定其水平受细胞周期蛋白T2或细胞周期蛋白T1调节的基因组。我们使用shRNA慢病毒载体稳定地耗尽HeLa细胞中的细胞周期蛋白T2或细胞周期蛋白T1。从这些细胞中提取的总RNA进行cDNA微阵列分析。我们发现，与用对照慢病毒转导的细胞相比，292个基因通过细胞周期蛋白T2的消耗而下调，631个基因通过细胞周期蛋白T1的消耗而下调。100个基因的表达通常在任一敲低中降低。此外，当细胞周期蛋白T2或细胞周期蛋白T1被耗尽时，分别有111和287个基因上调，共有45个基因。这些结果表明，有有限的冗余基因调控的细胞周期蛋白T1或细胞周期蛋白T2。
The elongation phase, like other steps of transcription by RNA Polymerase II, is subject to regulation. The positive transcription elongation factor b (P-TEFb) complex allows for the transition of mRNA synthesis to the productive elongation phase. P-TEFb contains Cdk9 (Cyclin-dependent kinase 9) as its catalytic subunit and is regulated by its Cyclin partners, Cyclin T1 and Cyclin T2. The HIV-1 Tat transactivator protein enhances viral gene expression by exclusively recruiting the Cdk9-Cyclin T1 P-TEFb complex to a RNA element in nascent viral transcripts called TAR. The expression patterns of Cyclin T1 and Cyclin T2 in primary monocytes and CD4+ T cells suggests that Cyclin T2 may be generally involved in expression of constitutively expressed genes in quiescent cells, while Cyclin T1 may be involved in expression of genes up-regulated during macrophage differentiation, T cell activation, and conditions of increased metabolic activity To investigate this issue, we wished to identify the sets of genes whose levels are regulated by either Cyclin T2 or Cyclin T1. We used shRNA lentiviral vectors to stably deplete either Cyclin T2 or Cyclin T1 in HeLa cells. Total RNA extracted from these cells was subjected to cDNA microarray analysis. We found that 292 genes were down- regulated by depletion of Cyclin T2 and 631 genes were down-regulated by depletion of Cyclin T1 compared to cells transduced with a control lentivirus. Expression of 100 genes was commonly reduced in either knockdown. Additionally, 111 and 287 genes were up-regulated when either Cyclin T2 or Cyclin T1 was depleted, respectively, with 45 genes in common. These results suggest that there is limited redundancy in genes regulated by Cyclin T1 or Cyclin T2.