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

0570972 - ÚMG 2024 RIV CH eng J - Journal Article
Balaban, Can - Sztacho, Martin - Antiga, Ludovica - Miladinović, Ana - Harata, M. - Hozák, Pavel
PIP2-Effector Protein MPRIP Regulates RNA Polymerase II Condensation and Transcription.
Biomolecules. Roč. 13, č. 3 (2023), č. článku 426. E-ISSN 2218-273X
R&D Projects: GA ČR GA19-05608S; GA ČR(CZ) GA18-19714S; GA MŠMT LTC19048; GA MŠMT LTC20024; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT(CZ) LM2018129; GA MŠMT(CZ) EF16_013/0001775
EU Projects: European Commission(XE) CA19105 - EpiLipidNET
Institutional support: RVO:68378050
Keywords : pip2 * RNA polymerase II * transcription * phase separation * mprip
OECD category: Biochemistry and molecular biology
Impact factor: 5.5, year: 2022
Method of publishing: Open access
https://www.mdpi.com/2218-273X/13/3/426

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.
Permanent Link: https://hdl.handle.net/11104/0342301