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First published online 11 March 2008
doi: 10.1242/jcs.020982

Journal of Cell Science 121, 1014-1024 (2008)
Published by The Company of Biologists 2008
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Research Article

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

Chi W. Tang1,*, Apolinar Maya-Mendoza1,*, Catherine Martin1, Kang Zeng1, Songbi Chen1, Dorota Feret2, Stuart A. Wilson3 and Dean A. Jackson1,{ddagger}

1 Faculty of Life Sciences, University of Manchester, MIB, 131 Princess Street, Manchester, M1 7DN, UK
2 Cancer Research UK, Paterson Institute for Cancer Research, Christie Hospital, Wilmslow Road, Manchester, M20 9BX, UK
3 Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, UK

{ddagger} Author for correspondence (e-mail: dean.jackson{at}manchester.ac.uk)

Accepted 9 January 2008

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.

Key words: Nuclear lamin proteins, Nucleoskeleton, Nuclear organisation, RNA synthesis, Chromosome territories






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