title: An intranuclear frame for chromatin compartmentalization and higher-order folding.
abstract: Recent ultrastructural, immunoelectron, and confocal microscopy observations done in our laboratory [Barboro et al. [2002] Exp. Cell. Res. 279:202-218] have confirmed that lamins and the nuclear mitotic apparatus protein (NuMA) are localized inside the interphase nucleus in a polymerized form. This provided evidence of the existence of a RNA stabilized lamin/NuMA frame, consisting of a web of thin ( approximately 3 and approximately 5 nm) lamin filaments to which NuMA is anchored mainly in the form of discrete islands, which might correspond to the minilattices described by Harborth et al. [1999] (EMBO. J. 18:1689-1700). In this article we propose that this scaffold is involved in the compartmentalization of both chromatin and functional domains and further determines the higher-order nuclear organization. This hypothesis is strongly supported by the scrutiny of different structural transitions which occur inside the nucleus, such as chromatin displacement and rearrangements, the collapse of the internal nuclear matrix after RNA digestion and the disruption of chromosome territories induced by RNase A and high salt treatment. All of these destructive events directly depend on the loss of the stabilizing effect exerted on the different levels of structural organization by the interaction of RNA with lamins and/or NuMA. Therefore, the integrity of nuclear RNA must be safeguarded as far as possible to isolate the matrix in the native form. This material will allow for the first time the unambiguous ultrastructural localization inside the INM of the components of the functional domains, so opening new avenues of investigation on the mechanisms of gene expression in eukaryotes.
authors.affiliation: Istituto Nazionale per la Ricerca sul Cancro, I-16132 Genova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Barboro
authors.forename: Cristina
authors.initials: C
authors.lastname: D'Arrigo
authors.forename: Michele
authors.initials: M
authors.lastname: Mormino
authors.forename: Rosella
authors.initials: R
authors.lastname: Coradeghini
authors.forename: Silvio
authors.initials: S
authors.lastname: Parodi
authors.forename: Eligio
authors.initials: E
authors.lastname: Patrone
authors.forename: Cecilia
authors.initials: C
authors.lastname: Balbi
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism* / Q000502:physiology*; D002875:Chromosomes / Q000648:ultrastructure; D006570:Heterochromatin / Q000737:chemistry*; D006801:Humans; D034882:Lamins / Q000378:metabolism; D015530:Nuclear Matrix / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D012313:RNA / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000494:pharmacology; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D002843:Chromatin; D006570:Heterochromatin; D034882:Lamins; D012313:RNA; D012259:Ribonuclease, Pancreatic