Medlin Joanne E, Uguen Patricia, Taylor Alice, Bentley David L, Murphy Shona
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
EMBO J. 2003 Feb 17;22(4):925-34. doi: 10.1093/emboj/cdg077.
The human snRNA genes transcribed by RNA polymerase II (e.g. U1 and U2) have a characteristic TATA-less promoter containing an essential proximal sequence element. Formation of the 3' end of these non-polyadenylated RNAs requires a specialized 3' box element whose function is promoter specific. Here we show that truncation of the C-terminal domain (CTD) of RNA polymerase II and treatment of cells with CTD kinase inhibitors, including DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole), causes a dramatic reduction in proper 3' end formation of U2 transcripts. Activation of 3' box recognition by the phosphorylated CTD would be consistent with the role of phospho-CTD in mRNA processing. CTD kinase inhibitors, however, have little effect on initiation or elongation of transcription of the U2 genes, whereas elongation of transcription of the beta-actin gene is severely affected. This result highlights differences in transcription of snRNA and mRNA genes.
由RNA聚合酶II转录的人类小核RNA(snRNA)基因(如U1和U2)具有一个特征性的无TATA启动子,其中包含一个必需的近端序列元件。这些非聚腺苷酸化RNA的3'端形成需要一个特殊的3'框元件,其功能具有启动子特异性。在这里,我们表明RNA聚合酶II的C末端结构域(CTD)的截短以及用包括DRB(5,6-二氯-1-β-D-呋喃核糖基苯并咪唑)在内的CTD激酶抑制剂处理细胞,会导致U2转录本正确的3'端形成显著减少。磷酸化的CTD对3'框识别的激活与磷酸化CTD在mRNA加工中的作用一致。然而,CTD激酶抑制剂对U2基因转录的起始或延伸影响很小,而β-肌动蛋白基因的转录延伸则受到严重影响。这一结果突出了snRNA和mRNA基因转录的差异。