Genome-wide RNAi selection identifies a regulator of transmission stage-enriched gene families and cell-type differentiation in Trypanosoma brucei

PLoS Pathogens

Eva Rico¹  Alasdair Ivens¹  Keith R. Matthews¹  Lucy Glover²  David Horn² 

[1]Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom

[2]The Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom

关键词: Trypanosoma;    RNA interference;    3' UTR;    Cell differentiation;    Trypanosoma brucei gambiense;    Gene expression;    Parasitic cell cycles;    Trypanosoma brucei;   

DOI  :  10.1371/journal.ppat.1006279

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Trypanosoma brucei, causing African sleeping-sickness, exploits quorum-sensing (QS) to generate the ‘stumpy forms’ necessary for the parasite’s transmission to tsetse-flies. These quiescent cells are generated by differentiation in the bloodstream from proliferative slender forms. Using genome-wide RNAi selection we screened for repressors of transmission stage-enriched mRNAs in slender forms, using the stumpy-elevated ESAG9 transcript as a model. This identified REG9.1, whose RNAi-silencing alleviated ESAG9 repression in slender forms and tsetse-midgut procyclic forms. Interestingly, trypanosome surface protein Family 5 and Family 7 mRNAs were also elevated, which, like ESAG9, are T. brucei specific and stumpy-enriched. We suggest these contribute to the distinct transmission biology and vector tropism of T. brucei from other African trypanosome species. As well as surface family regulation, REG9.1-depletion generated QS-independent development to stumpy forms in vivo, whereas REG9.1 overexpression in bloodstream forms potentiated spontaneous differentiation to procyclic forms in the absence of an external signal. Combined, this identifies REG9.1 as a regulator of developmental cell fate, controlling the expression of Trypanosoma brucei-specific molecules elevated during transmission.

【 授权许可】

CC BY