0604511 - ÚMG 2025 RIV US eng J - Článek v odborném periodiku
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
Grant CEP: 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
GRANT EU: European Commission(XE) CA19105 - EpiLipidNET
Grant ostatní: AV ČR(CZ) JSPS-20-06
Program: Bilaterální spolupráce
Institucionální podpora: RVO:68378050 ; RVO:67985904
Klíčová slova: long noncoding rnas * phase-separation * complex coacervation * prediction * regions * phosphoinositides * chromatin * domains * binding * organization
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 4, rok: 2023 ; AIS: 2.207, rok: 2023
Způsob publikování: Open access
Web výsledku:
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.
Trvalý link: https://hdl.handle.net/11104/0361941