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Nucleolar Architecture Is Modulated by a Small Molecule, the Inositol Pyrophosphate 5-InsP 7.
- Source :
-
Biomolecules (2218-273X) . Jan2023, Vol. 13 Issue 1, p153. 14p. - Publication Year :
- 2023
-
Abstract
- Inositol pyrophosphates (PP-InsPs); are a functionally diverse family of eukaryotic molecules that deploy a highly-specialized array of phosphate groups as a combinatorial cell-signaling code. One reductive strategy to derive a molecular-level understanding of the many actions of PP-InsPs is to individually characterize the proteins that bind them. Here, we describe an alternate approach that seeks a single, collective rationalization for PP-InsP binding to an entire group of proteins, i.e., the multiple nucleolar proteins previously reported to bind 5-InsP7 (5-diphospho-inositol-1,2,3,4,6-pentakisphosphate). Quantitative confocal imaging of the outer nucleolar granular region revealed its expansion when cellular 5-InsP7 levels were elevated by either (a) reducing the 5-InsP7 metabolism by a CRISPR-based knockout (KO) of either NUDT3 or PPIP5Ks; or (b), the heterologous expression of wild-type inositol hexakisphosphate kinase, i.e., IP6K2; separate expression of a kinase-dead IP6K2 mutant did not affect granular volume. Conversely, the nucleolar granular region in PPIP5K KO cells shrank back to the wild-type volume upon attenuating 5-InsP7 synthesis using either a pan-IP6K inhibitor or the siRNA-induced knockdown of IP6K1+IP6K2. Significantly, the inner fibrillar volume of the nucleolus was unaffected by 5-InsP7. We posit that 5-InsP7 acts as an 'electrostatic glue' that binds together positively charged surfaces on separate proteins, overcoming mutual protein–protein electrostatic repulsion the latter phenomenon is a known requirement for the assembly of a non-membranous biomolecular condensate. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SMALL molecules
*INOSITOL
*NUCLEAR proteins
*CRISPRS
*NUCLEOLUS
*NUCLEOPHOSMIN
Subjects
Details
- Language :
- English
- ISSN :
- 2218273X
- Volume :
- 13
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Biomolecules (2218-273X)
- Publication Type :
- Academic Journal
- Accession number :
- 161435740
- Full Text :
- https://doi.org/10.3390/biom13010153