Heix J, Zomerdijk J C, Ravanpay A, Tjian R, Grummt I
Division of Molecular Biology of the Cell II, German Cancer Research Center, Heidelberg.
Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1733-8. doi: 10.1073/pnas.94.5.1733.
Promoter selectivity for all three classes of eukaryotic RNA polymerases is brought about by multimeric protein complexes containing TATA box binding protein (TBP) and specific TBP-associated factors (TAFs). Unlike class II- and III-specific TBP-TAF complexes, the corresponding murine and human class I-specific transcription initiation factor TIF-IB/SL1 exhibits a pronounced selectivity for its homologous promoter. As a first step toward understanding the molecular basis of species-specific promoter recognition, we cloned the cDNAs encoding the three mouse pol I-specific TBP-associated factors (TAFIs) and compared the amino acid sequences of the murine TAFIs with their human counterparts. The four subunits from either species can form stable chimeric complexes that contain stoichiometric amounts of TBP and TAFIs, demonstrating that differences in the primary structure of human and mouse TAFIs do not dramatically alter the network of protein-protein contacts responsible for assembly of the multimeric complex. Thus, primate vs. rodent promoter selectivity mediated by the TBP-TAFI complex is likely to be the result of cumulative subtle differences between individual subunits that lead to species-specific properties of RNA polymerase I transcription.
所有三类真核生物RNA聚合酶的启动子选择性是由包含TATA框结合蛋白(TBP)和特定TBP相关因子(TAFs)的多聚体蛋白复合物实现的。与II类和III类特异性TBP-TAF复合物不同,相应的小鼠和人类I类特异性转录起始因子TIF-IB/SL1对其同源启动子表现出明显的选择性。作为理解物种特异性启动子识别分子基础的第一步,我们克隆了编码三种小鼠pol I特异性TBP相关因子(TAFIs)的cDNA,并将小鼠TAFIs的氨基酸序列与其人类对应物进行了比较。来自任一物种的四个亚基都可以形成稳定的嵌合复合物,其中含有化学计量的TBP和TAFIs,这表明人类和小鼠TAFIs一级结构的差异不会显著改变负责多聚体复合物组装的蛋白质-蛋白质接触网络。因此,由TBP-TAFI复合物介导的灵长类动物与啮齿动物启动子选择性可能是各个亚基之间累积细微差异的结果,这些差异导致了RNA聚合酶I转录的物种特异性特性。