The integrity of a lamin-B1-dependent nucleoskeleton is a fundamental determinant of RNA synthesis in human cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/58113
Title:
The integrity of a lamin-B1-dependent nucleoskeleton is a fundamental determinant of RNA synthesis in human cells.
Authors:
Tang, Chi W; Maya-Mendoza, Apolinar; Martin, Catherine; Zeng, Kang; Chen, Songbi; Feret, Dorota; Wilson, Stuart A; Jackson, Dean A
Abstract:
Spatial organisation of nuclear compartments is an important regulator of chromatin function, yet the molecular principles that maintain nuclear architecture remain ill-defined. We have used RNA interference to deplete key structural nuclear proteins, the nuclear lamins. In HeLa cells, we show that reduced expression of lamin B1, but not lamin A/C, severely inhibits RNA synthesis--first by RNA polymerase II and later by RNA polymerase I. Declining levels of transcription correlate with different morphological changes in major nuclear compartments, nucleoli and nuclear speckles. Ultimately, nuclear changes linked to the loss of synthetic activity result in expansion of the inter-chromatin domain and corresponding changes in the structure and spatial organisation of chromosome territories, which relocate towards the nuclear periphery. These results show that a lamin B1-containing nucleoskeleton is required to maintain RNA synthesis and that ongoing synthesis is a fundamental determinant of global nuclear architecture in mammalian cells.
Affiliation:
Faculty of Life Sciences, University of Manchester, MIB, 131 Princess Street, Manchester, M1 7DN, UK.
Citation:
The integrity of a lamin-B1-dependent nucleoskeleton is a fundamental determinant of RNA synthesis in human cells. 2008, 121 (Pt 7):1014-24 J. Cell. Sci.
Journal:
Journal of Cell Science
Issue Date:
1-Apr-2008
URI:
http://hdl.handle.net/10541/58113
DOI:
10.1242/jcs.020982
PubMed ID:
18334554
Type:
Article
Language:
en
ISSN:
0021-9533
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorTang, Chi W-
dc.contributor.authorMaya-Mendoza, Apolinar-
dc.contributor.authorMartin, Catherine-
dc.contributor.authorZeng, Kang-
dc.contributor.authorChen, Songbi-
dc.contributor.authorFeret, Dorota-
dc.contributor.authorWilson, Stuart A-
dc.contributor.authorJackson, Dean A-
dc.date.accessioned2009-03-31T11:08:21Z-
dc.date.available2009-03-31T11:08:21Z-
dc.date.issued2008-04-01-
dc.identifier.citationThe integrity of a lamin-B1-dependent nucleoskeleton is a fundamental determinant of RNA synthesis in human cells. 2008, 121 (Pt 7):1014-24 J. Cell. Sci.en
dc.identifier.issn0021-9533-
dc.identifier.pmid18334554-
dc.identifier.doi10.1242/jcs.020982-
dc.identifier.urihttp://hdl.handle.net/10541/58113-
dc.description.abstractSpatial organisation of nuclear compartments is an important regulator of chromatin function, yet the molecular principles that maintain nuclear architecture remain ill-defined. We have used RNA interference to deplete key structural nuclear proteins, the nuclear lamins. In HeLa cells, we show that reduced expression of lamin B1, but not lamin A/C, severely inhibits RNA synthesis--first by RNA polymerase II and later by RNA polymerase I. Declining levels of transcription correlate with different morphological changes in major nuclear compartments, nucleoli and nuclear speckles. Ultimately, nuclear changes linked to the loss of synthetic activity result in expansion of the inter-chromatin domain and corresponding changes in the structure and spatial organisation of chromosome territories, which relocate towards the nuclear periphery. These results show that a lamin B1-containing nucleoskeleton is required to maintain RNA synthesis and that ongoing synthesis is a fundamental determinant of global nuclear architecture in mammalian cells.en
dc.language.isoenen
dc.subjectNuclear Lamin Proteinsen
dc.subjectNucleoskeletonen
dc.subjectNuclear Organisationen
dc.subjectChromosome Territoriesen
dc.subject.meshApoptosis-
dc.subject.meshBlotting, Western-
dc.subject.meshCell Nucleus-
dc.subject.meshCells, Cultured-
dc.subject.meshFluorescent Antibody Technique-
dc.subject.meshHela Cells-
dc.subject.meshHumans-
dc.subject.meshIn Situ Hybridization, Fluorescence-
dc.subject.meshLamin Type A-
dc.subject.meshLamin Type B-
dc.subject.meshMicroscopy, Fluorescence-
dc.subject.meshNuclear Matrix-
dc.subject.meshRNA-
dc.subject.meshRNA Interference-
dc.subject.meshRNA Polymerase I-
dc.subject.meshRNA Polymerase II-
dc.titleThe integrity of a lamin-B1-dependent nucleoskeleton is a fundamental determinant of RNA synthesis in human cells.en
dc.typeArticleen
dc.contributor.departmentFaculty of Life Sciences, University of Manchester, MIB, 131 Princess Street, Manchester, M1 7DN, UK.en
dc.identifier.journalJournal of Cell Scienceen

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