Cell Reports (May 2024)
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. Späth,
- Ada Yonath,
- Shulamit Michaeli
Affiliations
- K. Shanmugha Rajan
- Department of Chemical and Structural Biology, The Weizmann Institute of Science, Rehovot 76100001, Israel; The Mina and Everard Goodman Faculty of Life Sciences and Advanced and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel
- Saurav Aryal
- The Mina and Everard Goodman Faculty of Life Sciences and Advanced and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel
- Disha-Gajanan Hiregange
- Department of Chemical and Structural Biology, The Weizmann Institute of Science, Rehovot 76100001, Israel
- Anat Bashan
- Department of Chemical and Structural Biology, The Weizmann Institute of Science, Rehovot 76100001, Israel
- Hava Madmoni
- The Mina and Everard Goodman Faculty of Life Sciences and Advanced and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel
- Mika Olami
- The Mina and Everard Goodman Faculty of Life Sciences and Advanced and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel
- Tirza Doniger
- The Mina and Everard Goodman Faculty of Life Sciences and Advanced and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel
- Smadar Cohen-Chalamish
- The Mina and Everard Goodman Faculty of Life Sciences and Advanced and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel
- Pascal Pescher
- Institut Pasteur, Université Paris Cité, INSERM U1201, Unité de Parasitologie moléculaire et Signalisation, Paris, France
- Masato Taoka
- Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Minami-osawa 1-1, Hachioji-shi, Tokyo 192-0397, Japan
- Yuko Nobe
- Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Minami-osawa 1-1, Hachioji-shi, Tokyo 192-0397, Japan
- Aliza Fedorenko
- Department of Chemical and Structural Biology, The Weizmann Institute of Science, Rehovot 76100001, Israel
- Tanaya Bose
- Department of Chemical and Structural Biology, The Weizmann Institute of Science, Rehovot 76100001, Israel
- Ella Zimermann
- Department of Chemical and Structural Biology, The Weizmann Institute of Science, Rehovot 76100001, Israel
- Eric Prina
- Institut Pasteur, Université Paris Cité, INSERM U1201, Unité de Parasitologie moléculaire et Signalisation, Paris, France
- Noa Aharon-Hefetz
- Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
- Yitzhak Pilpel
- Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
- Toshiaki Isobe
- Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Minami-osawa 1-1, Hachioji-shi, Tokyo 192-0397, Japan
- Ron Unger
- The Mina and Everard Goodman Faculty of Life Sciences and Advanced and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel
- Gerald F. Späth
- Institut Pasteur, Université Paris Cité, INSERM U1201, Unité de Parasitologie moléculaire et Signalisation, Paris, France
- Ada Yonath
- Department of Chemical and Structural Biology, The Weizmann Institute of Science, Rehovot 76100001, Israel
- Shulamit Michaeli
- The Mina and Everard Goodman Faculty of Life Sciences and Advanced and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel; Corresponding author
- Journal volume & issue
-
Vol. 43,
no. 5
p. 114203
Abstract
Summary: 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.
