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

Luke Maishman, Samson O. Obado, Sam Alsford, Jean Bart, Wei-Ming Chen, Alexander V. Ratushny, Miguel Navarro, David Horn, John D. Aitchison, Brian T. Chait, Michael P. Rout, Mark C. Field (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)10554-10570
Number of pages17
JournalNucleic Acids Research
Volume44
Issue number22
Early online date12 Sep 2016
DOIs
Publication statusPublished - Dec 2016

Keywords

  • Trypanosoma brucei
  • nuclear lamina
  • epigenetics
  • evolution
  • gene expression
  • heterochromatin
  • VSG

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