Department of Dermatology and Allergic Diseases, University of Ulm, James-Franck Ring N27, 89081 Ulm, Germany.
Nucleic Acids Res. 2012 Jan;40(2):650-9. doi: 10.1093/nar/gkr746. Epub 2011 Sep 28.
TFIIH is a multisubunit factor essential for transcription initiation and promoter escape of RNA polymerase II and for the opening of damaged DNA double strands in nucleotide excision repair (NER). In this study, we have analyzed at which step of the transcription cycle TFIIH is essential for transcription by RNA polymerase I. We demonstrate that TFIIH associates with the rDNA promoter and gene-internal sequences and leaves the rDNA promoter in a complex with RNA polymerase I after start of transcription. Moreover, mutations in the TFIIH subunits XPB and XPD found in Cockayne syndrome impair the interaction of TFIIH with the rDNA, but do not influence initiation complex formation or promoter escape of RNA polymerase I, but preclude the productivity of the enzyme by reducing transcription elongation in vivo and in vitro. Our results implicate that reduced RNA polymerase I transcription elongation and ribosomal stress could be one factor contributing to the Cockayne syndrome phenotype.
TFIIH 是一种多亚基因子，对于 RNA 聚合酶 II 的转录起始和启动子逃逸以及核苷酸切除修复 (NER) 中受损 DNA 双链的打开至关重要。在这项研究中，我们分析了 TFIIH 在 RNA 聚合酶 I 的转录循环的哪个步骤对于转录是必不可少的。我们证明，TFIIH 与 rDNA 启动子和基因内部序列结合，并在转录开始后与 RNA 聚合酶 I 一起离开 rDNA 启动子。此外，在 Cockayne 综合征中发现的 TFIIH 亚基 XPB 和 XPD 的突变会损害 TFIIH 与 rDNA 的相互作用，但不会影响起始复合物的形成或 RNA 聚合酶 I 的启动子逃逸，而是通过减少体内和体外转录延伸来阻碍酶的生产力。我们的结果表明，降低的 RNA 聚合酶 I 转录延伸和核糖体应激可能是导致 Cockayne 综合征表型的一个因素。
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