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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.

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


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.

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