4.8 Article

A long noncoding RNA promotes parasite differentiation in African trypanosomes

Journal

SCIENCE ADVANCES
Volume 8, Issue 24, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abn2706

Keywords

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Funding

  1. Fundacao para a Ciencia e Tecnologia (FCT) [PTDC/DTPEPI/7099/2014]
  2. Howard Hughes Medical Institute International Early Career Scientist Program [55007419]
  3. European Research Council [771714]
  4. la Caixa Foundation [LCF/PR/HR20/52400019, HR20-00361]
  5. FCT [IF/01050/2014]
  6. CEEC institutional program [CEECINST/00110/2018]
  7. Spanish Ministry of Economy, Industry and Competitiveness (MEIC)
  8. Centro de Excelencia Severo Ochoa
  9. CERCA Programme/Generalitat de Catalunya
  10. Israel Science Foundation [1959/20]
  11. U.S. Binational Science Foundation [2015/219]
  12. National Science Center SONATA BIS [492777, UMO-2020/38/E/NZ2/00372]
  13. National Science Center OPUS grant [UMO-2019/33/B/NZ2/01773, 443521]
  14. European Union [810425]
  15. European Research Council (ERC) [771714] Funding Source: European Research Council (ERC)

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This study identified 1428 previously uncharacterized lncRNA genes in the T. brucei genome. The key regulator, grumpy lncRNA, was found to promote parasite differentiation into the quiescent stumpy form, with this function being promoted by the encoded small nucleolar RNA. Overexpression of grumpy reduced parasitemia in infected mice.
The parasite Trypanosoma brucei causes African sleeping sickness that is fatal to patients if untreated. Parasite differentiation from a replicative slender form into a quiescent stumpy form promotes host survival and parasite transmission. Long noncoding RNAs (lncRNAs) are known to regulate cell differentiation in other eukaryotes. To determine whether lncRNAs are also involved in parasite differentiation, we used RNA sequencing to survey the T. brucei genome, identifying 1428 previously uncharacterized lncRNA genes. We find that grumpy lncRNA is a key regulator that promotes parasite differentiation into the quiescent stumpy form. This function is promoted by a small nucleolar RNA encoded within the grumpy lncRNA. snoGRUMPY binds to messenger RNAs of at least two stumpy regulatory genes, promoting their expression. grumpy overexpression reduces parasitemia in infected mice. Our analyses suggest that T. brucei lncRNAs modulate parasite-host interactions and provide a mechanism by which grumpy regulates cell differentiation in trypanosomes.

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