Rtr1 is a CTD phosphatase that regulates RNA polymerase II during the transition from serine 5 to serine 2 phosphorylation.

Rtr1 is a CTD phosphatase that regulates RNA polymerase II during the transition from serine 5 to serine 2 phosphorylation.
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DOI:
10.1016/j.molcel.2009.02.025
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发表时间:
2009-04-24
期刊:
影响因子:
16
通讯作者:
Washburn, Michael P.
Washburn, Michael P.
中科院分区:
生物学1区
文献类型:
--
作者:
Mosley, Amber L.;Pattenden, Samantha G.;Carey, Michael;Venkatesh, Swaminathan;Gilmore, Joshua M.;Florens, Laurence;Workman, Jerry L.;Washburn, Michael P.

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信使RNA加工通过协调募集Rpb1 c端结构域(CTD)的辅助蛋白与RNA聚合酶II (RNAPII)转录相耦合。转录延伸过程中CTD磷酸化的动态变化负责它们的招募,丝氨酸5磷酸化(S5-P)发生在基因的5 ‘端,丝氨酸2磷酸化(S2-P)发生在基因的3 ’端。负责调节S5-P和S2-P CTD之间过渡状态的蛋白质仍然难以捉摸。我们发现一个功能未知的保守蛋白Rtr1位于编码区,其最大富集水平发生在S5-P和S2-P RNAPII的峰之间。在Rtr1缺失后,RNAPII的S5-P形式在整个细胞提取物和整个编码区积累;此外,RNAPII转录减少,并观察到终止缺陷。Rtr1的功能表征揭示了它作为CTD磷酸酶在S5-到S2- P转化过程中所必需的作用。
Messenger RNA processing is coupled to RNA Polymerase II (RNAPII) transcription through coordinated recruitment of accessory proteins to the Rpb1 C-terminal domain (CTD). Dynamic changes in CTD phosphorylation during transcription elongation are responsible for their recruitment, with serine 5 phosphorylation (S5-P) occurring towards the 5’ end of genes and serine 2 phosphorylation (S2-P) occurring towards the 3’ end. The proteins responsible for regulation of the transition state between S5-P and S2-P CTD remain elusive. We show that a conserved protein of unknown function, Rtr1, localizes within coding regions, with maximum levels of enrichment occurring between the peaks of S5-P and S2-P RNAPII. Upon deletion of Rtr1, the S5-P form of RNAPII accumulates in both whole cell extracts and throughout coding regions; additionally, RNAPII transcription is decreased and termination defects are observed. Functional characterization of Rtr1 reveals its role as a CTD phosphatase essential for the S5- to S2- P transition.
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