Identification and functional implications of pseudouridine RNA modification on small noncoding RNAs in the mammalian pathogen Trypanosoma brucei

K. Shanmugha Rajan, Katerina Adler, Tirza Doniger, Smadar Cohen-Chalamish, Noa Aharon-Hefetz, Saurav Aryal, Yitzhak Pilpel, Christian Tschudi, Ron Unger, Shulamit Michaeli

Research output: Contribution to journalArticlepeer-review

Abstract

Trypanosoma brucei, the parasite that causes sleeping sickness, cycles between an insect and a mammalian host. However, the effect of RNA modifications such as pseudouridinylation on its ability to survive in these two different host environments is unclear. Here, two genome-wide approaches were applied for mapping pseudouridinylation sites (Ψs) on small nucleolar RNA (snoRNA), 7SL RNA, vault RNA, and tRNAs from T. brucei. We show using HydraPsiSeq and RiboMeth-seq that the Ψ on C/D snoRNA guiding 2′-O-methylation increased the efficiency of the guided modification on its target, rRNA. We found differential levels of Ψs on these noncoding RNAs in the two life stages (insect host and mammalian host) of the parasite. Furthermore, tRNA isoform abundance and Ψ modifications were characterized in these two life stages demonstrating stage-specific regulation. We conclude that the differential Ψ modifications identified here may contribute to modulating the function of noncoding RNAs involved in rRNA processing, rRNA modification, protein synthesis, and protein translocation during cycling of the parasite between its two hosts.

Original languageEnglish
Article number102141
Number of pages17
JournalJournal of Biological Chemistry
Volume298
Issue number7
DOIs
StatePublished - Jul 2022

Keywords

  • 2′-O-methylation
  • 7SL RNA
  • noncoding RNA
  • pseudouridine
  • snoRNA
  • tRNA
  • vtRNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry
  • Cell Biology

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