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Publication Abstract from PubMed

Leishmania is the causative agent of cutaneous and visceral diseases affecting millions of individuals worldwide. Pseudouridine (Psi), the most abundant modification on rRNA, changes during the parasite life cycle. Alterations in the level of a specific Psi in helix 69 (H69) affected ribosome function. To decipher the molecular mechanism of this phenotype, we determine the structure of ribosomes lacking the single Psi and its parental strain at approximately 2.4-3 A resolution using cryo-EM. Our findings demonstrate the significance of a single Psi 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.

Structural and mechanistic insights into the function of Leishmania ribosome lacking a single pseudouridine modification.,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, Spath GF, Yonath A, Michaeli S Cell Rep. 2024 May 28;43(5):114203. doi: 10.1016/j.celrep.2024.114203. Epub 2024 , May 8. PMID:38722744^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.