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Two Distinct Domains in Staf To Selectively Activate Small Nuclear RNA-Type and mRNA Promoters

机译：工作人员中的两个不同域，以选择性激活小核RNA类型和mRNA启动子。

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Staf is a transcriptional activator of prime importance for enhanced transcription of small nuclear (snRNA) and snRNA-type genes transcribed by RNA polymerases II and III (Pol II and III). In addition to this activity, it also possesses the capacity to stimulate expression from an RNA polymerase II mRNA promoter. This promiscuous activator thus provides a useful model system for studying the mechanism by which one single transcription factor can activate a large variety of promoters. Here, we report the use of in vivo assays to identify the Staf activation domains involved in promoter selectivity. Analysis of Staf mutants reveals the existence of two physically and functionally distinct regions, outside of the DNA binding domain, responsible for mediating selective transcriptional activation. While a 93-amino-acid domain, with the striking presence of four repeated units, is specialized for transcriptional activation of an mRNA promoter, a segment of only 18 amino acids, with a critical Leu-213 residue, acts specifically on Pol II and Pol III snRNA and snRNA-type promoters. In addition, this study disclosed the fundamental importance of invariant leucine and aspartic acid residues located in each repeat unit of the mRNA activation domain. Staf is therefore the first transcriptional activator described so far to harbor two physically and functionally distinct activator domains. This finding suggests that the same activator can contact different, specialized transcription complexes formed on different types of basal promoters through promoter-specific transactivation pathways.
机译：Staf是转录激活剂，对于增强RNA聚合酶II和III（Pol II和III）转录的小核（snRNA）和snRNA型基因的转录至关重要。除此活性外，它还具有刺激RNA聚合酶II mRNA启动子表达的能力。因此，这种混杂激活因子提供了一种有用的模型系统，用于研究一个转录因子可以激活多种启动子的机制。在这里，我们报告使用体内测定法来鉴定参与启动子选择性的Staf激活域。对Staf突变体的分析表明，在DNA结合域之外，存在两个物理和功能不同的区域，负责介导选择性转录激活。虽然一个具有93个氨基酸的结构域（具有四个重复单元的显着存在）专门用于mRNA启动子的转录激活，但只有18个氨基酸的片段具有关键的Leu-213残基，专门作用于Pol II和Pol III snRNA和snRNA型启动子。此外，这项研究揭示了位于mRNA激活域每个重复单元中的恒定亮氨酸和天冬氨酸残基的根本重要性。因此，Staf是迄今为止描述的第一个具有两个物理和功能上不同的激活域的转录激活因子。这一发现表明，相同的激活剂可以通过启动子特异性反式激活途径接触在不同类型的基础启动子上形成的不同的，专门的转录复合物。

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