Zhang Yijun, Fan Miaomiao, Zhang Xue, Huang Feng, Wu Kang, Zhang Junsong, Liu Jun, Huang Zhuoqiong, Luo Haihua, Tao Liang, Zhang Hui
Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
RNA. 2014 Dec;20(12):1878-89. doi: 10.1261/rna.045633.114. Epub 2014 Oct 21.
The TATA box represents one of the most prevalent core promoters where the pre-initiation complexes (PICs) for gene transcription are assembled. This assembly is crucial for transcription initiation and well regulated. Here we show that some cellular microRNAs (miRNAs) are associated with RNA polymerase II (Pol II) and TATA box-binding protein (TBP) in human peripheral blood mononuclear cells (PBMCs). Among them, let-7i sequence specifically binds to the TATA-box motif of interleukin-2 (IL-2) gene and elevates IL-2 mRNA and protein production in CD4(+) T-lymphocytes in vitro and in vivo. Through direct interaction with the TATA-box motif, let-7i facilitates the PIC assembly and transcription initiation of IL-2 promoter. Several other cellular miRNAs, such as mir-138, mir-92a or mir-181d, also enhance the promoter activities via binding to the TATA-box motifs of insulin, calcitonin or c-myc, respectively. In agreement with the finding that an HIV-1-encoded miRNA could enhance viral replication through targeting the viral promoter TATA-box motif, our data demonstrate that the interaction with core transcription machinery is a novel mechanism for miRNAs to regulate gene expression.
TATA 框是最普遍的核心启动子之一,基因转录的起始前复合物(PIC)在此处组装。这种组装对于转录起始至关重要且受到良好调控。在此我们表明,在人外周血单核细胞(PBMC)中,一些细胞微小RNA(miRNA)与RNA聚合酶II(Pol II)和TATA框结合蛋白(TBP)相关联。其中,let-7i序列特异性结合白细胞介素-2(IL-2)基因的TATA框基序,并在体外和体内提高CD4(+) T淋巴细胞中IL-2 mRNA和蛋白的产生。通过与TATA框基序直接相互作用,let-7i促进了IL-2启动子的PIC组装和转录起始。其他几种细胞miRNA,如mir-138、mir-92a或mir-181d,也分别通过与胰岛素、降钙素或c-myc的TATA框基序结合来增强启动子活性。与HIV-1编码的miRNA可通过靶向病毒启动子TATA框基序增强病毒复制这一发现一致,我们的数据表明,与核心转录机制的相互作用是miRNA调控基因表达的一种新机制。