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Título

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

AutorMaishman, Luke; Obado, Samson O.; Alsford, Sam; Bart, Jean-Mathieu; Chen, Wei-Ming; Ratushny, Alexander V.; Navarro, M.; Horn, David; Aitchison, John D.; Chait, Brian T.; Rout, Michael P.; Field, Mark C.
Fecha de publicación12-sep-2016
EditorOxford University Press
CitaciónNucleic Acids Research
ResumenThe 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.
DescripciónSupplementary Data are available at NAR Online.
Versión del editorhttps://academic.oup.com/nar/article/44/22/10554/2691330
URIhttp://hdl.handle.net/10261/175882
DOI10.1093/nar/gkw751
ISSN0305-1048
E-ISSN1362-4962
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