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

Nucleic Acids Res. 2016 Dec 15;44(22):10554-10570. doi: 10.1093/nar/gkw751. Epub 2016 Sep 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromosomes / genetics
  • Chromosomes / metabolism
  • DNA Damage
  • Gene Expression Regulation
  • Nuclear Lamina / physiology*
  • Nuclear Lamina / ultrastructure
  • Nuclear Pore / metabolism
  • Nuclear Pore / ultrastructure
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism*
  • Protein Transport
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Transcriptome
  • Trypanosoma brucei brucei / genetics
  • Trypanosoma brucei brucei / metabolism*
  • Trypanosoma brucei brucei / ultrastructure


  • Nuclear Pore Complex Proteins
  • Protozoan Proteins