PIP2-Effector Protein MPRIP Regulates RNA Polymerase II Condensation and Transcription.
PIP2-Effector Protein MPRIP Regulates RNA Polymerase II Condensation and Transcription.
复制标题
DOI：
10.3390/biom13030426
复制
发表时间：
2023-02-24
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
RNA聚合酶II （RNAPII）的Rpb1亚基c端结构域（CTD）的特定翻译后修饰与转录的不同阶段相关。该结构域Ser5残基的磷酸化与通过液-液相分离（LLPS）形成的引发缩合物有关。随后CTD的Tyr1磷酸化在启动子-近端区域达到峰值，并参与RNAPII的暂停释放。通过超分辨率显微镜技术，我们之前报道了核磷脂酰肌醇4,5-二磷酸（PIP2）与ser5磷酸化的RNAPII复合物结合并促进RNAPII转录。在这项研究中，我们发现肌球蛋白磷酸酶rho相互作用蛋白（MPRIP）是RNAPII转录的一种新的调节剂，可以将tyr1磷酸化的CTD （Tyr1P-CTD）招募到含有pip2的核结构中。MPRIP的缺失增加了起始凝聚物的数量，表明转录存在缺陷。我们假设MPRIP通过影响RNAPII复合物与核pip2 -富结构的关联来调节缩合和转录。鉴定Tyr1P-CTD作为PIP2和MPRIP的相互作用进一步指出了在RNAPII暂停释放中的调节作用，其中转录复合物离开起始凝聚物的易感性取决于其与核PIP2-富结构的关联。此外，负责与Tyr1P-CTD相互作用的MPRIP的n端结构域包含一个f -肌动蛋白结合区，这可以解释核f -肌动蛋白的形成如何影响RNAPII的转录和凝聚。总的来说，我们的研究结果通过鉴定f -肌动蛋白结合蛋白MPRIP作为转录调节剂和RNAPII缩合的决定因素，揭示了PIP2在RNAPII转录中的作用。
The specific post-translational modifications of the C-terminal domain (CTD) of the Rpb1 subunit of RNA polymerase II (RNAPII) correlate with different stages of transcription. The phosphorylation of the Ser5 residues of this domain associates with the initiation condensates, which are formed through liquid-liquid phase separation (LLPS). The subsequent Tyr1 phosphorylation of the CTD peaks at the promoter-proximal region and is involved in the pause-release of RNAPII. By implementing super-resolution microscopy techniques, we previously reported that the nuclear Phosphatidylinositol 4,5-bisphosphate (PIP2) associates with the Ser5-phosphorylated-RNAPII complex and facilitates the RNAPII transcription. In this study, we identified Myosin Phosphatase Rho-Interacting Protein (MPRIP) as a novel regulator of the RNAPII transcription that recruits Tyr1-phosphorylated CTD (Tyr1P-CTD) to nuclear PIP2-containing structures. The depletion of MPRIP increases the number of the initiation condensates, indicating a defect in the transcription. We hypothesize that MPRIP regulates the condensation and transcription through affecting the association of the RNAPII complex with nuclear PIP2-rich structures. The identification of Tyr1P-CTD as an interactor of PIP2 and MPRIP further points to a regulatory role in RNAPII pause-release, where the susceptibility of the transcriptional complex to leave the initiation condensate depends on its association with nuclear PIP2-rich structures. Moreover, the N-terminal domain of MPRIP, which is responsible for the interaction with the Tyr1P-CTD, contains an F-actin binding region that offers an explanation of how nuclear F-actin formations can affect the RNAPII transcription and condensation. Overall, our findings shed light on the role of PIP2 in RNAPII transcription through identifying the F-actin binding protein MPRIP as a transcription regulator and a determinant of the condensation of RNAPII.
登录
查看更多内容
影响因子：
1.9
作者：
Hoboth P;Šebesta O;Sztacho M;Castano E;Hozák P
通讯作者：
Hozák P
DOI：
10.1038/nrm.2017.63
发表时间：
2017-10
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Herzel L;Ottoz DSM;Alpert T;Neugebauer KM
通讯作者：
Neugebauer KM
影响因子：
7.7
作者：
Cho, Won-Ki;Jayanth, Namrata;Cisse, Ibrahim I.
通讯作者：
Cisse, Ibrahim I.
影响因子：
56.9
作者：
Baarlink, Christian;Wang, Haicui;Grosse, Robert
通讯作者：
Grosse, Robert
影响因子：
56.9
作者：
Chen, Xizi;Qi, Yilun;Xu, Yanhui
通讯作者：
Xu, Yanhui