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Post-transcriptional reprogramming by thousands of mRNA untranslated regions in trypanosomes

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  • Anna Trenaman

    (University of Dundee)

  • Michele Tinti

    (University of Dundee)

  • Richard J. Wall

    (University of Dundee
    London School of Hygiene & Tropical Medicine)

  • David Horn

    (University of Dundee)

Abstract

Although genome-wide polycistronic transcription places major emphasis on post-transcriptional controls in trypanosomatids, messenger RNA cis-regulatory untranslated regions (UTRs) have remained largely uncharacterised. Here, we describe a genome-scale massive parallel reporter assay coupled with 3’-UTR-seq profiling in the African trypanosome and identify thousands of regulatory UTRs. Increased translation efficiency was associated with dosage of adenine-rich poly-purine tracts (pPuTs). An independent assessment of native UTRs using machine learning based predictions confirmed the robust correspondence between pPuTs and positive control, as did an assessment of synthetic UTRs. Those 3’-UTRs associated with upregulated expression in bloodstream-stage cells were also enriched in uracil-rich poly-pyrimidine tracts, suggesting a mechanism for developmental activation through pPuT ‘unmasking’. Thus, we describe a cis-regulatory UTR sequence ‘code’ that underpins gene expression control in the context of a constitutively transcribed genome. We conclude that thousands of UTRs post-transcriptionally reprogram gene expression profiles in trypanosomes.

Suggested Citation

  • Anna Trenaman & Michele Tinti & Richard J. Wall & David Horn, 2024. "Post-transcriptional reprogramming by thousands of mRNA untranslated regions in trypanosomes," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52432-0
    DOI: 10.1038/s41467-024-52432-0
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    References listed on IDEAS

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    1. Binny M. Mony & Paula MacGregor & Alasdair Ivens & Federico Rojas & Andrew Cowton & Julie Young & David Horn & Keith Matthews, 2014. "Genome-wide dissection of the quorum sensing signalling pathway in Trypanosoma brucei," Nature, Nature, vol. 505(7485), pages 681-685, January.
    2. Emma M. Briggs & Federico Rojas & Richard McCulloch & Keith R. Matthews & Thomas D. Otto, 2021. "Single-cell transcriptomic analysis of bloodstream Trypanosoma brucei reconstructs cell cycle progression and developmental quorum sensing," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    3. Björn Schwanhäusser & Dorothea Busse & Na Li & Gunnar Dittmar & Johannes Schuchhardt & Jana Wolf & Wei Chen & Matthias Selbach, 2011. "Global quantification of mammalian gene expression control," Nature, Nature, vol. 473(7347), pages 337-342, May.
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