Mason Paul B, Struhl Kevin
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Cell. 2005 Mar 18;17(6):831-40. doi: 10.1016/j.molcel.2005.02.017.
A number of proteins and drugs have been implicated in the process of transcriptional elongation by RNA polymerase (Pol) II, but the factors that govern the elongation rate (nucleotide additions per min) and processivity (nucleotide additions per initiation event) in vivo are poorly understood. Here, we show that a mutation in the Rpb2 subunit of Pol II reduces both the elongation rate and processivity in vivo. In contrast, none of the putative elongation factors tested affect the elongation rate, although mutations in the THO complex and in Spt4 significantly reduce processivity. The drugs 6-azauracil and mycophenolic acid reduce both the elongation rate and processivity, and this processivity defect is aggravated by mutations in Spt4, TFIIS, and CTDK-1. Our results suggest that, in vivo, a reduced rate of Pol II elongation leads to premature dissociation along the chromatin template and that Pol II processivity can be uncoupled from elongation rate.
许多蛋白质和药物都与RNA聚合酶（Pol）II的转录延伸过程有关，但对于体内控制延伸速率（每分钟添加的核苷酸数）和持续性（每次起始事件添加的核苷酸数）的因素，我们了解甚少。在这里，我们表明Pol II的Rpb2亚基中的突变会降低体内的延伸速率和持续性。相比之下，尽管THO复合物和Spt4中的突变会显著降低持续性，但所测试的假定延伸因子均不影响延伸速率。药物6-氮尿嘧啶和霉酚酸会降低延伸速率和持续性，并且Spt4、TFIIS和CTDK-1中的突变会加剧这种持续性缺陷。我们的结果表明，在体内，Pol II延伸速率降低会导致沿染色质模板的过早解离，并且Pol II的持续性可以与延伸速率解偶联。
