Kimura Hiroshi, Sugaya Kimihiko, Cook Peter R
Sir William Dunn School of Pathology, Oxford OX1 3RE, UK.
J Cell Biol. 2002 Dec 9;159(5):777-82. doi: 10.1083/jcb.200206019.
RNA polymerase II transcribes most eukaryotic genes. Its catalytic subunit was tagged with green fluorescent protein and expressed in Chinese hamster cells bearing a mutation in the same subunit; it complemented the defect and so was functional. Photobleaching revealed two kinetic fractions of polymerase in living nuclei: approximately 75% moved rapidly, but approximately 25% was transiently immobile (association t1/2 approximately 20 min) and transcriptionally active, as incubation with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole eliminated it. No immobile but inactive fraction was detected, providing little support for the existence of a stable holoenzyme, or the slow stepwise assembly of a preinitiation complex on promoters or the nuclear substructure. Actinomycin D decreased the rapidly moving fraction, suggesting that engaged polymerases stall at intercalated molecules while others initiate. When wild-type cells containing only the endogenous enzyme were incubated with [3H]uridine, nascent transcripts became saturated with tritium with similar kinetics (t1/2 approximately 14 min). These data are consistent with a polymerase being mobile for one half to five sixths of a transcription cycle, and rapid assembly into the preinitiation complex. Then, most expressed transcription units would spend significant times unassociated with engaged polymerases.
RNA聚合酶II转录大多数真核基因。其催化亚基用绿色荧光蛋白标记,并在同一亚基发生突变的中国仓鼠细胞中表达;它弥补了缺陷,因此具有功能。光漂白显示活细胞核中聚合酶有两个动力学组分:约75%快速移动,但约25%暂时固定不动(结合半衰期约20分钟)且具有转录活性,因为用5,6-二氯-1-β-D-呋喃核糖基苯并咪唑孵育可消除它。未检测到固定但无活性的组分,这几乎不支持稳定全酶的存在,或启动子或核亚结构上预起始复合物的缓慢逐步组装。放线菌素D减少了快速移动的组分,表明正在转录的聚合酶在插入分子处停滞,而其他聚合酶开始转录。当仅含有内源性酶的野生型细胞用[3H]尿苷孵育时,新生转录本以相似的动力学(半衰期约14分钟)被氚饱和。这些数据与聚合酶在转录周期的二分之一到六分之五时间内处于移动状态,并快速组装成预起始复合物一致。然后,大多数表达的转录单位会有相当长的时间与正在转录的聚合酶不相关。