Ser7 phosphorylation of the CTD recruits the RPAP2 Ser5 phosphatase to snRNA genes.

Ser7 phosphorylation of the CTD recruits the RPAP2 Ser5 phosphatase to snRNA genes.
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DOI:
10.1016/j.molcel.2011.11.006
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发表时间:
2012-01-13
期刊:
影响因子:
16
通讯作者:
Murphy, Shona
Murphy, Shona
中科院分区:
生物学1区
文献类型:
--
作者:
Egloff, Sylvain;Zaborowska, Justyna;Laitem, Clelia;Kiss, Tames;Murphy, Shona

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RNA 聚合酶 II (Pol II) 大亚基的羧基末端结构域 (CTD) 包含共有 Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 的多个七肽重复序列。转录周期中 Ser2、Ser5 和 Ser7 的可逆磷酸化介导转录/RNA 加工因子的顺序募集。 Ser7 的磷酸化对于将基因类型特异性整合复合物募集至 Pol II 转录的小核 (sn)RNA 基因是必需的。在这里,我们证明 RNA Pol II 相关蛋白 2 (RPAP2) 特异性识别 Pol II CTD 上的磷酸化 Ser7 标记,并且还与整合子亚基相互作用。 siRNA 介导的 RPAP2 敲低和 Ser7 突变为丙氨酸会导致 snRNA 基因表达的类似缺陷。此外,我们还证明 RPAP2 是一种 CTD Ser5 磷酸酶。综上所述,我们的结果表明,在 snRNA 基因转录过程中,Ser7 磷酸化促进了 RPAP2 的募集,而 RPAP2 又募集了 Integrator 并使 Ser5 去磷酸化。 ► RPAP2 与 Pol II 和 snRNA 基因特异性整合复合物相互作用 ► RPAP2 识别 Pol II CTD 上的 Ser7P 标记 ► RPAP2 是 snRNA 和蛋白质编码基因表达所必需的 ► RPAP2 是 Ser5P 特异性 CTD 磷酸酶
The carboxy-terminal domain (CTD) of the large subunit of RNA polymerase II (Pol II) comprises multiple heptapeptide repeats of the consensus Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. Reversible phosphorylation of Ser2, Ser5, and Ser7 during the transcription cycle mediates the sequential recruitment of transcription/RNA processing factors. Phosphorylation of Ser7 is required for recruitment of the gene type-specific Integrator complex to the Pol II-transcribed small nuclear (sn)RNA genes. Here, we show that RNA Pol II-associated protein 2 (RPAP2) specifically recognizes the phospho-Ser7 mark on the Pol II CTD and also interacts with Integrator subunits. siRNA-mediated knockdown of RPAP2 and mutation of Ser7 to alanine cause similar defects in snRNA gene expression. In addition, we show that RPAP2 is a CTD Ser5 phosphatase. Taken together, our results indicate that during transcription of snRNA genes, Ser7 phosphorylation facilitates recruitment of RPAP2, which in turn both recruits Integrator and dephosphorylates Ser5. ► RPAP2 interacts both with Pol II and the snRNA gene-specific Integrator complex ► RPAP2 recognizes the Ser7P mark on the Pol II CTD ► RPAP2 is required for expression of snRNA and protein-coding genes ► RPAP2 is a Ser5P-specific CTD phosphatase
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