PIP2-Effector Protein MPRIP Regulates RNA Polymerase II Condensation and Transcription

DOI Web Site 参考文献69件 オープンアクセス
  • Can Balaban
    Department of Biology of the Cell Nucleus, Institute of Molecular Genetics of the Czech Academy of Sciences, 142 20 Prague, Czech Republic
  • Martin Sztacho
    Department of Biology of the Cell Nucleus, Institute of Molecular Genetics of the Czech Academy of Sciences, 142 20 Prague, Czech Republic
  • Ludovica Antiga
    Department of Biology of the Cell Nucleus, Institute of Molecular Genetics of the Czech Academy of Sciences, 142 20 Prague, Czech Republic
  • Ana Miladinović
    Department of Biology of the Cell Nucleus, Institute of Molecular Genetics of the Czech Academy of Sciences, 142 20 Prague, Czech Republic
  • Masahiko Harata
    Laboratory of Molecular Biochemistry, Division of Life Science, Graduate School of Agricultural Science, Tohoku University, 468-1, Aramaki Aza Aoba, Aoba-ku, Sendai 980-0845, Japan
  • Pavel Hozák
    Department of Biology of the Cell Nucleus, Institute of Molecular Genetics of the Czech Academy of Sciences, 142 20 Prague, Czech Republic

抄録

<jats:p>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.</jats:p>

収録刊行物

  • Biomolecules

    Biomolecules 13 (3), 426-, 2023-02-24

    MDPI AG

参考文献 (69)*注記

もっと見る

関連プロジェクト

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ