title: Nuclear Functions of Nucleolin through Global Proteomics and Interactomic Approaches.
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.
authors.affiliation: International Center for Infectiology Research (CIRI), Inserm U1111, CNRS UMR5308 , 69007 Lyon, France.|Ecole Normale Supérieure de Lyon , 69007 Lyon, France.|Labex Ecofect Université de Lyon , 69007 Lyon, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Salvetti
authors.affiliation: Université Grenoble Alpes , 38000 Grenoble, France.|CEA, BIG-BGE , 38000 Grenoble, France.|INSERM, BGE , 38000 Grenoble, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Couté
authors.affiliation: International Center for Infectiology Research (CIRI), Inserm U1111, CNRS UMR5308 , 69007 Lyon, France.|Ecole Normale Supérieure de Lyon , 69007 Lyon, France.|Labex Ecofect Université de Lyon , 69007 Lyon, France.
authors.forename: Alberto
authors.initials: A
authors.lastname: Epstein
authors.affiliation: Subdepartment of Molecular Genetics, Public Health Institute of Chile , Santiago, Chile.
authors.forename: Loredana
authors.initials: L
authors.lastname: Arata
authors.affiliation: Université Grenoble Alpes , 38000 Grenoble, France.|CEA, BIG-BGE , 38000 Grenoble, France.|INSERM, BGE , 38000 Grenoble, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kraut
authors.affiliation: Pôle Rhône Alpes de Bioinformatique (PRABI), Université Lyon 1 , 69100 Villeurbanne, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Navratil
authors.affiliation: Ecole Normale Supérieure de Lyon , 69007 Lyon, France.|Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052, CNRS UMR5286 , 69003 Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouvet
authors.affiliation: International Center for Infectiology Research (CIRI), Inserm U1111, CNRS UMR5308 , 69007 Lyon, France.|Ecole Normale Supérieure de Lyon , 69007 Lyon, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Greco
mesh_terms: D063326:Exosome Multienzyme Ribonuclease Complex / Q000737:chemistry; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D040901:Proteomics / Q000379:methods*; D020365:RNA Helicases / Q000378:metabolism; D020871:RNA Stability; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D012270:Ribosomes; D000097796:Nucleolin
chemical_list: D063326:Exosome Multienzyme Ribonuclease Complex; D009687:Nuclear Proteins; D010750:Phosphoproteins; D020365:RNA Helicases; D016601:RNA-Binding Proteins; D000097796:Nucleolin
keywords: mRNA processing; nucleolin; proteomics; tandem affinity purification