The interaction between nucleophosmin/NPM1 and the large ribosomal subunit precursors contribute to maintaining the nucleolar structure

Nucleoli are sites where both the large and small ribosomal subunits mature. Biochemical assays have suggested that a multivalent nucleolar protein, NPM1/nucleophosmin contributes to the formation of the outer layer of the nucleolus. Prior works show that NPM1 depletion disorganizes the nucleolar st...

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Bibliographic Details
Published in:Biochimica et biophysica acta. Molecular cell research 2021-01, Vol.1868 (1), p.118879-118879, Article 118879
Main Authors: Okuwaki, Mitsuru, Saito, Shoko, Hirawake-Mogi, Hiroko, Nagata, Kyosuke
Format: Article
Language:English
Subjects:
Cell Nucleolus - genetics
Genes, rRNA - genetics
Nuclear Proteins - genetics
Nucleolus
Nucleophosmin
Protein Binding - genetics
Proteomics - methods
Ribosomal Proteins - genetics
Ribosome biogenesis
Ribosome Subunits, Large - genetics
Ribosomes - genetics
rRNA
rRNA processing
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Summary:Nucleoli are sites where both the large and small ribosomal subunits mature. Biochemical assays have suggested that a multivalent nucleolar protein, NPM1/nucleophosmin contributes to the formation of the outer layer of the nucleolus. Prior works show that NPM1 depletion disorganizes the nucleolar structure. However, the mechanism of how NPM1 regulates the nucleolar structure has been unknown. We demonstrated that NPM1 directly interacts with the large ribosomal subunits and maintains them in the nucleolus. Ectopically localized NPM1 efficiently recruits only the large ribosomal subunit precursors, while ectopically localized large ribosomal subunit by the ribosomal protein RPL4 efficiently recruits NPM1. These results suggest that the nucleolar localization of NPM1 and the large ribosomal subunit precursors are mutually dependent. Furthermore, proteomic and localization analyses suggest that NPM1 plays a crucial role in the accumulation of the late processing machinery of the large ribosomal subunits in the nucleolus. Our results suggest that NPM1 maintains the pre-ribosomes and assembly machinery in the nucleolus, which in turn determines the nucleolar volume. •NPM1 depletion changed the GC region of the nucleolus.•NPM1 directly interacts with the 60S ribosomal subunits.•NPM1 depletion decreased the nucleolar accumulation of the pre-60S subunits and a subset of pre-60S processing factors.•NPM1 depletion inhibits the 32S pre-rRNA processing.
ISSN:0167-4889
1879-2596
DOI:10.1016/j.bbamcr.2020.118879