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PreprintCited by 5Trypanosoma species research and implicationsRNA Research and SplicingResearch on Leishmaniasis Studies

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Differentiation granules, a dynamic regulator of T. brucei development.

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Cayla, Mathieu, Spanos, Christos, Waskett, Eliza, Rappsilber, Juri, Matthews, Keith·2023·Nature Communications
DOI 10.21203/rs.3.rs-3442788/v1PMC PMC10998879

Preprint — published as 10.1038/s41467-024-47309-1 · Paper page

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Abstract

Adaptation to a change of environment is an essential process for survival, in particular for parasitic organisms exposed to a wide range of hosts. Such adaptations include rapid control of gene expression through the formation of membraneless organelles composed of poly-A RNA and proteins. The African trypanosome Trypanosoma brucei is exquisitely sensitive to well-defined environmental stimuli that trigger cellular adaptations through differentiation events that characterise its complex life cycle. The parasite has been shown to form stress granules in vitro and it has been proposed that such a stress response could have been repurposed to enable differentiation and facilitate parasite transmission. Therefore, we explored the composition and positional dynamics of membraneless granules formed in response to starvation stress and during differentiation in the mammalian host between the replicative slender and transmission adapted stumpy forms. We find that T. brucei differentiation does not reflect the default response to environmental stress. Instead, the developmental response of the parasites involves a specific and programmed hierarchy of membraneless granule assembly, with distinct components and regulation by protein kinases such as TbDYRK, that are required for the parasite to successfully progress through its life cycle development and prepare for transmission.

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Metadata

Authors
Cayla, M., Spanos, C., Waskett, E., Rappsilber, J., & Matthews, K.
Affiliations
  • University of York (GB)
  • Wellcome Centre for Cell Biology (GB)
  • University of Edinburgh (GB)
Corresponding author
Cayla, Mathieu
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-10-20
Volume
15
Issue
1
Pages
2972-2972
ISSN
2041-1723 (ISSN-L)
DOI
10.21203/rs.3.rs-3442788/v1
PMC
PMC10998879
OpenAlex
W4394011034
Cited by
5
References
1
Citations by year
2026: 3 · 2025: 1 · 2024: 1
FWCI
1.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (221717, 103740, 108504, 103740/Z/14/Z)
  • Wolfson Foundation (WM140045)
  • Medical Research Council (MR/W026996/1)
  • European and Developing Countries Clinical Trials Partnership
Topics
  • Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
Keywords
Trypanosoma brucei, stress granules, biomolecular condensates, polyadenylated RNA, parasite differentiation, life cycle development, gene expression regulation
MeSH terms
Animals, Mammals, Trypanosoma, Trypanosoma brucei brucei

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