SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes

Andreu Saura, Paula A. Iribarren, Domingo Rojas-Barros, Jean M. Bart, Diana López-Farfán, Eduardo Andrés-León, Isabel Vidal-Cobo, Cordula Boehm, Vanina E. Alvarez, Mark C. Field, Miguel Navarro (Lead / Corresponding author)

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Abstract

SUMOylation is a post-translational modification that positively regulates monoallelic expression of the trypanosome variant surface glycoprotein (VSG). The presence of a highly SUMOylated focus associated with the nuclear body, where the VSG gene is transcribed, further suggests an important role of SUMOylation in regulating VSG expression. Here, we show that SNF2PH, a SUMOylated plant homeodomain (PH)-transcription factor, is upregulated in the bloodstream form of the parasite and enriched at the active VSG telomere. SUMOylation promotes the recruitment of SNF2PH to the VSG promoter, where it is required to maintain RNA polymerase I and thus to regulate VSG transcript levels. Further, ectopic overexpression of SNF2PH in insect forms, but not of a mutant lacking the PH domain, induces the expression of bloodstream stage-specific surface proteins. These data suggest that SNF2PH SUMOylation positively regulates VSG monoallelic transcription, while the PH domain is required for the expression of bloodstream-specific surface proteins. Thus, SNF2PH functions as a positive activator, linking expression of infective form surface proteins and VSG regulation, thereby acting as a major regulator of pathogenicity.

Original languageEnglish
Article numbere48029
Pages (from-to)1-18
Number of pages18
JournalEMBO Reports
Early online date6 Nov 2019
DOIs
Publication statusE-pub ahead of print - 6 Nov 2019

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Trypanosomiasis
Membrane Glycoproteins
Sumoylation
Membrane Proteins
RNA Polymerase I
Telomere
Transcription
Post Translational Protein Processing
Virulence
Insects
Parasites
Transcription Factors
Genes

Keywords

  • SUMO
  • antigenic variation
  • plant homeodomain
  • post-translational modification
  • variant surface glycoprotein

Cite this

Saura, A., Iribarren, P. A., Rojas-Barros, D., Bart, J. M., López-Farfán, D., Andrés-León, E., ... Navarro, M. (2019). SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes. EMBO Reports, 1-18. [e48029]. https://doi.org/10.15252/embr.201948029
Saura, Andreu ; Iribarren, Paula A. ; Rojas-Barros, Domingo ; Bart, Jean M. ; López-Farfán, Diana ; Andrés-León, Eduardo ; Vidal-Cobo, Isabel ; Boehm, Cordula ; Alvarez, Vanina E. ; Field, Mark C. ; Navarro, Miguel. / SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes. In: EMBO Reports. 2019 ; pp. 1-18.
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Saura, A, Iribarren, PA, Rojas-Barros, D, Bart, JM, López-Farfán, D, Andrés-León, E, Vidal-Cobo, I, Boehm, C, Alvarez, VE, Field, MC & Navarro, M 2019, 'SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes', EMBO Reports, pp. 1-18. https://doi.org/10.15252/embr.201948029

SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes. / Saura, Andreu; Iribarren, Paula A.; Rojas-Barros, Domingo; Bart, Jean M.; López-Farfán, Diana; Andrés-León, Eduardo; Vidal-Cobo, Isabel; Boehm, Cordula; Alvarez, Vanina E.; Field, Mark C.; Navarro, Miguel (Lead / Corresponding author).

In: EMBO Reports, 06.11.2019, p. 1-18.

Research output: Contribution to journalArticle

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T1 - SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes

AU - Saura, Andreu

AU - Iribarren, Paula A.

AU - Rojas-Barros, Domingo

AU - Bart, Jean M.

AU - López-Farfán, Diana

AU - Andrés-León, Eduardo

AU - Vidal-Cobo, Isabel

AU - Boehm, Cordula

AU - Alvarez, Vanina E.

AU - Field, Mark C.

AU - Navarro, Miguel

PY - 2019/11/6

Y1 - 2019/11/6

N2 - SUMOylation is a post-translational modification that positively regulates monoallelic expression of the trypanosome variant surface glycoprotein (VSG). The presence of a highly SUMOylated focus associated with the nuclear body, where the VSG gene is transcribed, further suggests an important role of SUMOylation in regulating VSG expression. Here, we show that SNF2PH, a SUMOylated plant homeodomain (PH)-transcription factor, is upregulated in the bloodstream form of the parasite and enriched at the active VSG telomere. SUMOylation promotes the recruitment of SNF2PH to the VSG promoter, where it is required to maintain RNA polymerase I and thus to regulate VSG transcript levels. Further, ectopic overexpression of SNF2PH in insect forms, but not of a mutant lacking the PH domain, induces the expression of bloodstream stage-specific surface proteins. These data suggest that SNF2PH SUMOylation positively regulates VSG monoallelic transcription, while the PH domain is required for the expression of bloodstream-specific surface proteins. Thus, SNF2PH functions as a positive activator, linking expression of infective form surface proteins and VSG regulation, thereby acting as a major regulator of pathogenicity.

AB - SUMOylation is a post-translational modification that positively regulates monoallelic expression of the trypanosome variant surface glycoprotein (VSG). The presence of a highly SUMOylated focus associated with the nuclear body, where the VSG gene is transcribed, further suggests an important role of SUMOylation in regulating VSG expression. Here, we show that SNF2PH, a SUMOylated plant homeodomain (PH)-transcription factor, is upregulated in the bloodstream form of the parasite and enriched at the active VSG telomere. SUMOylation promotes the recruitment of SNF2PH to the VSG promoter, where it is required to maintain RNA polymerase I and thus to regulate VSG transcript levels. Further, ectopic overexpression of SNF2PH in insect forms, but not of a mutant lacking the PH domain, induces the expression of bloodstream stage-specific surface proteins. These data suggest that SNF2PH SUMOylation positively regulates VSG monoallelic transcription, while the PH domain is required for the expression of bloodstream-specific surface proteins. Thus, SNF2PH functions as a positive activator, linking expression of infective form surface proteins and VSG regulation, thereby acting as a major regulator of pathogenicity.

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Saura A, Iribarren PA, Rojas-Barros D, Bart JM, López-Farfán D, Andrés-León E et al. SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes. EMBO Reports. 2019 Nov 6;1-18. e48029. https://doi.org/10.15252/embr.201948029