Pseudouridines on Trypanosoma brucei mRNAs are developmentally regulated: Implications to mRNA stability and protein binding

K. Shanmugha Rajan, Katerina Adler, Hava Madmoni, Dana Peleg-Chen, Smadar Cohen-Chalamish, Tirza Doniger, Beathrice Galili, Doron Gerber, Ron Unger, Christian Tschudi, Shulamit Michaeli

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The parasite Trypanosoma brucei cycles between an insect and a mammalian host and is the causative agent of sleeping sickness. Here, we performed high-throughput mapping of pseudouridines (Ψs) on mRNA from two life stages of the parasite. The analysis revealed ~273 Ψs, including developmentally regulated Ψs that are guided by homologs of pseudouridine synthases (PUS1, 3, 5, and 7). Mutating the U that undergoes pseudouridylation in the 3′ UTR of valyl-tRNA synthetase destabilized the mRNA level. To investigate the mechanism by which Ψ affects the stability of this mRNA, proteins that bind to the 3′ UTR were identified, including the RNA binding protein RBSR1. The binding of RBSR1 protein to the 3′ UTR was stronger when lacking Ψ compared to transcripts carrying the modification, suggesting that Ψ can inhibit the binding of proteins to their target and thus affect the stability of mRNAs. Consequently, Ψ modification on mRNA adds an additional level of regulation to the dominant post-transcriptional control in these parasites.

Original languageEnglish
Pages (from-to)808-826
Number of pages19
JournalMolecular Microbiology
Issue number3
StatePublished - Sep 2021

Bibliographical note

Funding Information:
This work was supported by a grant from the Israel‐US Binational Science Foundation (BSF). S.M. holds the David and Inez Myers Chair in RNA silencing of diseases.

Publisher Copyright:
© 2021 John Wiley & Sons Ltd


  • PUS enzymes
  • pseudouridine (Ψ)
  • trypanosomes
  • Ψ protein interaction
  • Ψ-seq on mRNAs


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