title: Compartmentalization and Functionality of Nuclear Disorder: Intrinsic Disorder and Protein-Protein Interactions in Intra-Nuclear Compartments.
abstract: The cell nucleus contains a number of membrane-less organelles or intra-nuclear compartments. These compartments are dynamic structures representing liquid-droplet phases which are only slightly denser than the bulk intra-nuclear fluid. They possess different functions, have diverse morphologies, and are typically composed of RNA (or, in some cases, DNA) and proteins. We analyzed 3005 mouse proteins localized in specific intra-nuclear organelles, such as nucleolus, chromatin, Cajal bodies, nuclear speckles, promyelocytic leukemia (PML) nuclear bodies, nuclear lamina, nuclear pores, and perinuclear compartment and compared them with ~29,863 non-nuclear proteins from mouse proteome. Our analysis revealed that intrinsic disorder is enriched in the majority of intra-nuclear compartments, except for the nuclear pore and lamina. These compartments are depleted in proteins that lack disordered domains and enriched in proteins that have multiple disordered domains. Moonlighting proteins found in multiple intra-nuclear compartments are more likely to have multiple disordered domains. Protein-protein interaction networks in the intra-nuclear compartments are denser and include more hubs compared to the non-nuclear proteins. Hubs in the intra-nuclear compartments (except for the nuclear pore) are enriched in disorder compared with non-nuclear hubs and non-nuclear proteins. Therefore, our work provides support to the idea of the functional importance of intrinsic disorder in the cell nucleus and shows that many proteins associated with sub-nuclear organelles in nuclei of mouse cells are enriched in disorder. This high level of disorder in the mouse nuclear proteins defines their ability to serve as very promiscuous binders, possessing both large quantities of potential disorder-based interaction sites and the ability of a single such site to be involved in a large number of interactions.
authors.affiliation: Department of Electrical and Computer Engineering, University of Alberta, Edmonton, AB T6G 2V4, Canada. fanchi@ualberta.ca.
authors.forename: Fanchi
authors.initials: F
authors.lastname: Meng
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA. ina2@health.usf.edu.
authors.forename: Insung
authors.initials: I
authors.lastname: Na
authors.affiliation: Department of Electrical and Computer Engineering, University of Alberta, Edmonton, AB T6G 2V4, Canada. lkurgan@ualberta.ca.|Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23219, USA. lkurgan@ualberta.ca.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kurgan
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA. vuversky@health.usf.edu.|University of South Florida Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA. vuversky@health.usf.edu.|Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow Region 142292, Russian. vuversky@health.usf.edu.|Biology Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia. vuversky@health.usf.edu.|Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russian. vuversky@health.usf.edu.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D064267:Intrinsically Disordered Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D020543:Proteome / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D064267:Intrinsically Disordered Proteins; D020543:Proteome; D016601:RNA-Binding Proteins
keywords: DNA-binding protein; RNA-binding protein; cell nucleus; intra-nuclear compartments; intrinsically disordered protein; membrane-less organelles