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Targeting of RNA Polymerase II by a nuclear Legionella pneumophila Dot/Icm effector SnpL


Schuelein, R; Spencer, H; Dagley, LF; Li, PF; Luo, L; Stow, JL; Abraham, G; Naderer, T; Gomez-Valero, L; Buchrieser, C; Sugimoto, C; Yamagishi, J; Webb, AI; Pasricha, S; Hartland, EL
2018-04-24
Cell Microbiol
Journal Article in press
The intracellular pathogen Legionella pneumophila influences numerous eukaryotic cellular processes through the Dot/Icm-dependent translocation of more than 300 effector proteins into the host cell. Although many translocated effectors localize to the Legionella replicative vacuole, other effectors can affect remote intracellular sites. Following infection, a subset of effector proteins localizes to the nucleus where they subvert host cell transcriptional responses to infection. Here we identified Lpg2519 (Lpp2587/Lpw27461), as a new nuclear-localized effector that we have termed SnpL. Upon ectopic expression or during L. pneumophila infection, SnpL showed strong nuclear localization by immunofluorescence microscopy but was excluded from nucleoli. Using immunoprecipitation and mass spectrometry, we determined the host-binding partner of SnpL as the eukaryotic transcription elongation factor, SUPT5H/Spt5. SUPT5H is an evolutionarily conserved component of the DRB sensitivity-inducing factor complex (DSIF complex) that regulates RNA polymerase II (Pol II) dependent mRNA processing and transcription elongation. Protein interaction studies showed that SnpL bound to the central KOW motif region of SUPT5H. Ectopic expression of SnpL led to massive upregulation of host gene expression and macrophage cell death. The activity of SnpL further highlights the ability of L. pneumophila to control fundamental eukaryotic processes such as transcription that, in the case of SnpL, leads to global upregulation of host gene expression.
Wiley
Systems Biology and Personalised Medicine
10.1111/cmi.12852
29691989
Refer to copyright notice on published article.