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

Authors :
Rajan KS
Aryal S
Hiregange DG
Bashan A
Madmoni H
Olami M
Doniger T
Cohen-Chalamish S
Pescher P
Taoka M
Nobe Y
Fedorenko A
Bose T
Zimermann E
Prina E
Aharon-Hefetz N
Pilpel Y
Isobe T
Unger R
Späth GF
Yonath A
Michaeli S
Source :
Cell reports [Cell Rep] 2024 May 28; Vol. 43 (5), pp. 114203. Date of Electronic Publication: 2024 May 08.
Publication Year :
2024

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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
2211-1247
Volume :
43
Issue :
5
Database :
MEDLINE
Journal :
Cell reports
Publication Type :
Academic Journal
Accession number :
38722744
Full Text :
https://doi.org/10.1016/j.celrep.2024.114203