Martin M P, Gerlach V L, Brow D A
Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, Wisconsin 53706-1532, USA.
Mol Cell Biol. 2001 Oct;21(19):6429-39. doi: 10.1128/MCB.21.19.6429-6439.2001.
The Saccharomyces cerevisiae U6 RNA gene, SNR6, possesses upstream sequences that allow productive binding in vitro of the RNA polymerase III (Pol III) transcription initiation factor IIIB (TFIIIB) in the absence of TFIIIC or other assembly factors. TFIIIC-independent transcription of SNR6 in vitro is highly sensitive to point mutations in a consensus TATA box at position -30. In contrast, the TATA box is dispensable for SNR6 transcription in vivo, apparently because TFIIIC bound to the intragenic A block and downstream B block can recruit TFIIIB via protein-protein interactions. A mutant allele of SNR6 with decreased spacing between the A and B blocks, snr6-Delta42, exhibits increased dependence on the upstream sequences in vivo. Unexpectedly, we find that in vivo expression of snr6-Delta42 is much more sensitive to mutations in a (dT-dA)(7) tract between the TATA box and transcription start site than to mutations in the TATA box itself. Inversion of single base pairs in the center of the dT-dA tract nearly abolishes transcription of snr6-Delta42, yet inversion of all 7 base pairs has little effect on expression, indicating that the dA-dT tract is relatively orientation independent. Although it is within the TFIIIB footprint, point mutations in the dT-dA tract do not inhibit TFIIIB binding or TFIIIC-independent transcription of SNR6 in vitro. In the absence of the chromatin architectural protein Nhp6, dT-dA tract mutations are lethal even when A-to-B block spacing is wild type. We conclude that the (dT-dA)(7) tract and Nhp6 cooperate to direct productive transcription complex assembly on SNR6 in vivo.
酿酒酵母U6 RNA基因SNR6拥有上游序列,这些序列能够在体外RNA聚合酶III(Pol III)转录起始因子IIIB(TFIIIB)不存在TFIIIC或其他组装因子的情况下进行有效结合。体外SNR6不依赖TFIIIC的转录对位于-30位置的共有TATA框中的点突变高度敏感。相比之下,TATA框在体内对SNR6转录是可有可无的,这显然是因为与基因内A块和下游B块结合的TFIIIC可以通过蛋白质-蛋白质相互作用招募TFIIIB。A块和B块之间间距减小的SNR6突变等位基因snr6-Δ42在体内对上游序列的依赖性增加。出乎意料的是,我们发现snr6-Δ42在体内的表达对TATA框和转录起始位点之间的(dT-dA)7序列中的突变比对TATA框本身的突变更敏感。dT-dA序列中心单个碱基对的倒置几乎完全消除了snr6-Δ42的转录,但所有7个碱基对的倒置对表达影响很小,这表明dA-dT序列相对不依赖方向。尽管它位于TFIIIB足迹内,但dT-dA序列中的点突变在体外并不抑制TFIIIB结合或SNR6不依赖TFIIIC的转录。在没有染色质结构蛋白Nhp6的情况下,即使A到B块间距为野生型,dT-dA序列突变也是致死的。我们得出结论,(dT-dA)7序列和Nhp6在体内协同作用,指导SNR6上有生产性的转录复合物组装。