哺乳动物RNA聚合酶II C末端结构域（CTD）非共有重复序列在CTD稳定性和细胞增殖中的作用。
Role of the mammalian RNA polymerase II C-terminal domain (CTD) nonconsensus repeats in CTD stability and cell proliferation.
作者信息
Chapman Rob D, Conrad Marcus, Eick Dirk
机构信息
GSF-Research Centre for Environment and Health, Institute for Clinical Molecular Biology and Tumour Genetics, Munich, Germany.
出版信息
Mol Cell Biol. 2005 Sep;25(17):7665-74. doi: 10.1128/MCB.25.17.7665-7674.2005.
Abstract
The C-terminal domain (CTD) of mammalian RNA polymerase II (Pol II) consists of 52 repeats of the consensus heptapeptide YSPTSPS and links transcription to the processing of pre-mRNA. The length of the CTD and the number of repeats diverging from the consensus sequence have increased through evolution, but their functional importance remains unknown. Here, we show that the deletion of repeats 1 to 3 or 52 leads to cleavage and degradation of the CTD from Pol II in vivo. Including these repeats, however, allowed the construction of stable, synthetic CTDs. To our surprise, polymerases consisting of just consensus repeats could support normal growth and viability of cells. We conclude that all other nonconsensus CTD repeats are dispensable for the transcription and pre-mRNA processing of genes essential for proliferation.
摘要
哺乳动物RNA聚合酶II（Pol II）的C末端结构域（CTD）由52个七肽共有序列YSPTSPS重复组成，它将转录与前体mRNA的加工联系起来。通过进化，CTD的长度以及与共有序列不同的重复序列数量有所增加，但其功能重要性仍不清楚。在这里，我们表明，体内重复序列1至3或52的缺失会导致CTD从Pol II上切割和降解。然而，包含这些重复序列能够构建稳定的合成CTD。令我们惊讶的是，仅由共有重复序列组成的聚合酶能够支持细胞的正常生长和存活。我们得出结论，所有其他非共有CTD重复序列对于增殖所必需基因的转录和前体mRNA加工而言是可有可无的。
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3
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Nature. 2004 Nov 25;432(7016):517-22. doi: 10.1038/nature03041.
4
Elongation by RNA polymerase II: the short and long of it.
Genes Dev. 2004 Oct 15;18(20):2437-68. doi: 10.1101/gad.1235904.
5
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RNA. 2004 Oct;10(10):1489-98. doi: 10.1261/rna.7100104.
6
The link between mRNA processing and transcription: communication works both ways.
Exp Cell Res. 2004 May 15;296(1):91-7. doi: 10.1016/j.yexcr.2004.03.019.
7
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8
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10
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