A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei

K. Shanmugha Rajan; Hava Madmoni; Anat Bashan; Masato Taoka; Saurav Aryal; Yuko Nobe; Tirza Doniger; Beathrice Galili Kostin; Amit Blumberg; Smadar Cohen-Chalamish; Schraga Schwartz; Andre Rivalta; Ella Zimmerman; Ron Unger; Toshiaki Isobe; Ada Yonath; Shulamit Michaeli

doi:10.1038/s41467-023-43263-6

A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei

K. Shanmugha Rajan
, Hava Madmoni
, Anat Bashan
, Masato Taoka
, Saurav Aryal
, Yuko Nobe
, Tirza Doniger
, Beathrice Galili Kostin
, Amit Blumberg
, Smadar Cohen-Chalamish
, Schraga Schwartz
, Andre Rivalta
, Ella Zimmerman
, Ron Unger
, Toshiaki Isobe
, Ada Yonath
, Shulamit Michaeli

Weizmann Institute of Science
Tokyo Metropolitan University

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Trypanosomes are protozoan parasites that cycle between insect and mammalian hosts and are the causative agent of sleeping sickness. Here, we describe the changes of pseudouridine (Ψ) modification on rRNA in the two life stages of the parasite using four different genome-wide approaches. CRISPR-Cas9 knock-outs of all four snoRNAs guiding Ψ on helix 69 (H69) of the large rRNA subunit were lethal. A single knock-out of a snoRNA guiding Ψ530 on H69 altered the composition of the 80S monosome. These changes specifically affected the translation of only a subset of proteins. This study correlates a single site Ψ modification with changes in ribosomal protein stoichiometry, supported by a high-resolution cryo-EM structure. We propose that alteration in rRNA modifications could generate ribosomes preferentially translating state-beneficial proteins.

Original language	English
Article number	7462
Number of pages	16
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-43263-6
State	Published - 20 Nov 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

Funding

This work was supported by a grant from the Israel Science Foundation (1959/20). S.M. holds the David and Inez Myers Chair in RNA silencing of diseases. K.S.R. is supported by the Dean of Faculty Fellowship, Koshland Prize and Sir Charles Clore Postdoctoral Fellowship from the Weizmann Institute. The authors want to thank Noa Aharon-Hefetz and Yitzhak Pilpel for their assistance in preparing the Supplementary Fig. 4.

Funders	Funder number
Koshland Prize and Sir Charles Clore
Weizmann Institute
Israel Science Foundation	1959/20

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/s41467-023-43263-6

Cite this

Rajan, K. S., Madmoni, H., Bashan, A., Taoka, M., Aryal, S., Nobe, Y., Doniger, T., Galili Kostin, B., Blumberg, A., Cohen-Chalamish, S., Schwartz, S., Rivalta, A., Zimmerman, E., Unger, R., Isobe, T., Yonath, A., & Michaeli, S. (2023). A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei. Nature Communications, 14(1), Article 7462. https://doi.org/10.1038/s41467-023-43263-6

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title = "A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei",

abstract = "Trypanosomes are protozoan parasites that cycle between insect and mammalian hosts and are the causative agent of sleeping sickness. Here, we describe the changes of pseudouridine (Ψ) modification on rRNA in the two life stages of the parasite using four different genome-wide approaches. CRISPR-Cas9 knock-outs of all four snoRNAs guiding Ψ on helix 69 (H69) of the large rRNA subunit were lethal. A single knock-out of a snoRNA guiding Ψ530 on H69 altered the composition of the 80S monosome. These changes specifically affected the translation of only a subset of proteins. This study correlates a single site Ψ modification with changes in ribosomal protein stoichiometry, supported by a high-resolution cryo-EM structure. We propose that alteration in rRNA modifications could generate ribosomes preferentially translating state-beneficial proteins.",

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Rajan, KS, Madmoni, H, Bashan, A, Taoka, M, Aryal, S, Nobe, Y, Doniger, T, Galili Kostin, B, Blumberg, A, Cohen-Chalamish, S, Schwartz, S, Rivalta, A, Zimmerman, E, Unger, R, Isobe, T, Yonath, A & Michaeli, S 2023, 'A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei', Nature Communications, vol. 14, no. 1, 7462. https://doi.org/10.1038/s41467-023-43263-6

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AU - Aryal, Saurav

AU - Nobe, Yuko

AU - Doniger, Tirza

AU - Galili Kostin, Beathrice

AU - Blumberg, Amit

AU - Cohen-Chalamish, Smadar

AU - Schwartz, Schraga

AU - Rivalta, Andre

AU - Zimmerman, Ella

AU - Unger, Ron

AU - Isobe, Toshiaki

AU - Yonath, Ada

AU - Michaeli, Shulamit

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AB - Trypanosomes are protozoan parasites that cycle between insect and mammalian hosts and are the causative agent of sleeping sickness. Here, we describe the changes of pseudouridine (Ψ) modification on rRNA in the two life stages of the parasite using four different genome-wide approaches. CRISPR-Cas9 knock-outs of all four snoRNAs guiding Ψ on helix 69 (H69) of the large rRNA subunit were lethal. A single knock-out of a snoRNA guiding Ψ530 on H69 altered the composition of the 80S monosome. These changes specifically affected the translation of only a subset of proteins. This study correlates a single site Ψ modification with changes in ribosomal protein stoichiometry, supported by a high-resolution cryo-EM structure. We propose that alteration in rRNA modifications could generate ribosomes preferentially translating state-beneficial proteins.

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A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei

Abstract

Bibliographical note

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A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei

Abstract

Bibliographical note

Funding

UN SDGs

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