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J Proteome Res. 2016 May 6;15(5):1659-69. doi: 10.1021/acs.jproteome.6b00126. Epub 2016 Apr 21.

Nuclear Functions of Nucleolin through Global Proteomics and Interactomic Approaches.

Author information

1
International Center for Infectiology Research (CIRI), Inserm U1111, CNRS UMR5308 , 69007 Lyon, France.
2
Ecole Normale Supérieure de Lyon , 69007 Lyon, France.
3
Labex Ecofect Université de Lyon , 69007 Lyon, France.
4
Université Grenoble Alpes , 38000 Grenoble, France.
5
CEA, BIG-BGE , 38000 Grenoble, France.
6
INSERM, BGE , 38000 Grenoble, France.
7
Subdepartment of Molecular Genetics, Public Health Institute of Chile , Santiago, Chile.
8
Pôle Rhône Alpes de Bioinformatique (PRABI), Université Lyon 1 , 69100 Villeurbanne, France.
9
Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052, CNRS UMR5286 , 69003 Lyon, France.

Abstract

Nucleolin (NCL) is a major component of the cell nucleolus, which has the ability to rapidly shuttle to several other cells' compartments. NCL plays important roles in a variety of essential functions, among which are ribosome biogenesis, gene expression, and cell growth. However, the precise mechanisms underlying NCL functions are still unclear. Our study aimed to provide new information on NCL functions via the identification of its nuclear interacting partners. Using an interactomics approach, we identified 140 proteins co-purified with NCL, among which 100 of them were specifically found to be associated with NCL after RNase digestion. The functional classification of these proteins confirmed the prominent role of NCL in ribosome biogenesis and additionally revealed the possible involvement of nuclear NCL in several pre-mRNA processing pathways through its interaction with RNA helicases and proteins participating in pre-mRNA splicing, transport, or stability. NCL knockdown experiments revealed that NCL regulates the localization of EXOSC10 and the amount of ZC3HAV1, two components of the RNA exosome, further suggesting its involvement in the control of mRNA stability. Altogether, this study describes the first nuclear interactome of human NCL and provides the basis for further understanding the mechanisms underlying the essential functions of this nucleolar protein.

KEYWORDS:

mRNA processing; nucleolin; proteomics; tandem affinity purification

PMID:
27049334
DOI:
10.1021/acs.jproteome.6b00126
[Indexed for MEDLINE]

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