Molecular insight into the mechanism of nuclear PIP2 regulation of RNA Polymerase II transcription

0555847 - ÚMG 2022 RIV CZ eng O - Ostatní výsledky
Sztacho, Martin - Balaban, Can - Šalovská, Barbora - Červenka, J. - Hozák, Pavel
Molecular insight into the mechanism of nuclear PIP2 regulation of RNA Polymerase II transcription.
2021
Grant CEP: 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
Výzkumná infrastruktura: Czech-BioImaging II - 90129
Institucionální podpora: RVO:68378050
Klíčová slova: Phosphoinositides * transcription * RNA polymerase II * phase separation
Obor OECD: Cell biology

Specific nuclear sub-compartments that are regions of fundamental processes such as gene expression or DNA repair, contain phosphoinositides (PIPs). PIPs potentially represent signals for the localization of specific proteins into different nuclear functional domains. We performed limited proteolysis followed by label-free quantitative mass spectrometry and identified nuclear protein effectors of phosphatidylinositol 4,5-bisphosphate (PIP2). We identified 515 proteins with PIP2-binding capacity. Gene ontology analysis revealed that these proteins are involved in regulation of Pol II, mRNA splicing, transport and cell cycle. They localize to non-membrane bound organelles and are connected to actin nucleoskeleton. We provided the evidence for presence of MPRIP, an F‐actin‐binding protein in the cell nucleus. The MPRIP protein binds to PIP2 and localizes to the nuclear speckles and nuclear lipid islets which are known to be involved in transcription. We identified MPRIP as a component of Pol2/Nuclear Myosin 1 complex and showed that MPRIP forms phase‐separated condensates which are able to bind nuclear F‐actin fibers. We propose a model where the PIP2/MPRIP association might contribute to the regulation of Pol2 transcription via phase separation and nuclear actin polymerization.
Trvalý link: http://hdl.handle.net/11104/0330304