0604511 - ÚMG 2025 RIV US eng J - Journal Article
Sztacho, Martin - Červenka, Jakub - Šalovská, Barbora - Antiga, Ludovica - Hoboth, Peter - Hozák, Pavel
The RNA-dependent association of phosphatidylinositol 4,5-bisphosphate with intrinsically disordered proteins contribute to nuclear compartmentalization.
PLoS Genetics. Roč. 20, č. 12 (2024), č. článku e1011462. ISSN 1553-7404. E-ISSN 1553-7404
R&D Projects: GA ČR GA19-05608S; GA ČR(CZ) GA18-19714S; GA MŠMT LX22NPO5102; GA MŠMT LTC19048; GA MŠMT LTC20024; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT(CZ) LM2018129; GA MŠMT(CZ) LM2023050; GA MŠMT(CZ) EF16_013/0001775; GA MŠMT(CZ) EF18_046/0016045
EU Projects: European Commission(XE) CA19105 - EpiLipidNET
Grant - others:AV ČR(CZ) JSPS-20-06
Program: Bilaterální spolupráce
Institutional support: RVO:68378050 ; RVO:67985904
Keywords : long noncoding rnas * phase-separation * complex coacervation * prediction * regions * phosphoinositides * chromatin * domains * binding * organization
OECD category: Biochemistry and molecular biology
Impact factor: 4, year: 2023 ; AIS: 2.207, rok: 2023
Method of publishing: Open access
Result website:
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1011462DOI: https://doi.org/10.1371/journal.pgen.1011462

The RNA content is crucial for the formation of nuclear compartments, such as nuclear speckles and nucleoli. Phosphatidylinositol 4,5-bisphosphate (PIP2) is found in nuclear speckles, nucleoli, and nuclear lipid islets and is involved in RNA polymerase I/II transcription. Intriguingly, the nuclear localization of PIP2 was also shown to be RNA-dependent. We therefore investigated whether PIP2 and RNA cooperate in the establishment of nuclear architecture. In this study, we unveiled the RNA-dependent PIP2-associated (RDPA) nuclear proteome in human cells by mass spectrometry. We found that intrinsically disordered regions (IDRs) with polybasic PIP2-binding K/R motifs are prevalent features of RDPA proteins. Moreover, these IDRs of RDPA proteins exhibit enrichment for phosphorylation, acetylation, and ubiquitination sites. Our results show for the first time that the RDPA protein Bromodomain-containing protein 4 (BRD4) associates with PIP2 in the RNA-dependent manner via electrostatic interactions, and that altered PIP2 levels affect the number of nuclear foci of BRD4 protein. Thus, we propose that PIP2 spatiotemporally orchestrates nuclear processes through association with RNA and RDPA proteins and affects their ability to form foci presumably via phase separation. This suggests the pivotal role of PIP2 in the establishment of a functional nuclear architecture competent for gene expression.
Permanent Link: https://hdl.handle.net/11104/0361941