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Nucleic Acids Res. 2016 Dec 15;44(22):10554-10570. Epub 2016 Sep 12.

Co-dependence between trypanosome nuclear lamina components in nuclear stability and control of gene expression.

Author information

1
School of Life Sciences, University of Dundee, Dundee, Scotland, DD1 5EH, UK.
2
The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
3
London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
4
Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Cientificas, 18100 Grenada, Spain.
5
Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), Seattle, WA 98109, USA.
6
Institute for Systems Biology, Seattle, WA 98109, USA.
7
School of Life Sciences, University of Dundee, Dundee, Scotland, DD1 5EH, UK mfield@mac.com.

Abstract

The nuclear lamina is a filamentous structure subtending the nuclear envelope and required for chromatin organization, transcriptional regulation and maintaining nuclear structure. The trypanosomatid coiled-coil NUP-1 protein is a lamina component functionally analogous to lamins, the major lamina proteins of metazoa. There is little evidence for shared ancestry, suggesting the presence of a distinct lamina system in trypanosomes. To find additional trypanosomatid lamina components we identified NUP-1 interacting proteins by affinity capture and mass-spectrometry. Multiple components of the nuclear pore complex (NPC) and a second coiled-coil protein, which we termed NUP-2, were found. NUP-2 has a punctate distribution at the nuclear periphery throughout the cell cycle and is in close proximity to NUP-1, the NPCs and telomeric chromosomal regions. RNAi-mediated silencing of NUP-2 leads to severe proliferation defects, gross alterations to nuclear structure, chromosomal organization and nuclear envelope architecture. Further, transcription is altered at telomere-proximal variant surface glycoprotein (VSG) expression sites (ESs), suggesting a role in controlling ES expression, although NUP-2 silencing does not increase VSG switching. Transcriptome analysis suggests specific alterations to Pol I-dependent transcription. NUP-1 is mislocalized in NUP-2 knockdown cells and vice versa, implying that NUP-1 and NUP-2 form a co-dependent network and identifying NUP-2 as a second trypanosomatid nuclear lamina component.

PMID:
27625397
PMCID:
PMC5159534
DOI:
10.1093/nar/gkw751
[Indexed for MEDLINE]
Free PMC Article

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