Structural and mechanistic insights into the function of Leishmania ribosome lacking a single pseudouridine modification

K. Shanmugha Rajan, Saurav Aryal, Disha Gajanan Hiregange, Anat Bashan, Hava Madmoni, Mika Olami, Tirza Doniger, Smadar Cohen-Chalamish, Pascal Pescher, Masato Taoka, Yuko Nobe, Aliza Fedorenko, Tanaya Bose, Ella Zimermann, Eric Prina, Noa Aharon-Hefetz, Yitzhak Pilpel, Toshiaki Isobe, Ron Unger, Gerald F. SpäthAda Yonath, Shulamit Michaeli

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Leishmania is the causative agent of cutaneous and visceral diseases affecting millions of individuals worldwide. Pseudouridine (Ψ), the most abundant modification on rRNA, changes during the parasite life cycle. Alterations in the level of a specific Ψ in helix 69 (H69) affected ribosome function. To decipher the molecular mechanism of this phenotype, we determine the structure of ribosomes lacking the single Ψ and its parental strain at ∼2.4–3 Å resolution using cryo-EM. Our findings demonstrate the significance of a single Ψ on H69 to its structure and the importance for its interactions with helix 44 and specific tRNAs. Our study suggests that rRNA modification affects translation of mRNAs carrying codon bias due to selective accommodation of tRNAs by the ribosome. Based on the high-resolution structures, we propose a mechanism explaining how the ribosome selects specific tRNAs.

Original languageEnglish
Article number114203
JournalCell Reports
Volume43
Issue number5
DOIs
StatePublished - 28 May 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Keywords

  • CP: Microbiology
  • CP: Molecular biology
  • Leishmania
  • RNA modification
  • codon bias
  • cryo-EM
  • pseudouridine
  • ribosome
  • snoRNA
  • tRNA
  • translation control

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