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TitleA single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 7462, Year 2023
Publish dateNov 20, 2023
AuthorsK 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 /
PubMed AbstractTrypanosomes 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 ...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.
External linksNat Commun / PubMed:37985661 / PubMed Central
MethodsEM (single particle)
Resolution2.47 - 2.6 Å
Structure data

EMDB-17208, PDB-8ova:
CRYO-EM STRUCTURE OF TRYPANOSOMA BRUCEI PROCYCLIC FORM 80S RIBOSOME : PARENTAL STRAIN
Method: EM (single particle) / Resolution: 2.47 Å

EMDB-17212, PDB-8ove:
CRYO-EM STRUCTURE OF TRYPANOSOMA BRUCEI PROCYCLIC FORM 80S RIBOSOME : TB11CS6H1 snoRNA mutant
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-17249: CRYO-EM CONSENSUS MAP OF TRYPANOSOMA BRUCEI PROCYCLIC FORM 80S RIBOSOME : PARENTAL STRAIN
PDB-8ova: CRYO-EM STRUCTURE OF TRYPANOSOMA BRUCEI PROCYCLIC FORM 80S RIBOSOME : PARENTAL STRAIN
Method: EM (single particle) / Resolution: 2.47 Å

EMDB-17250: CRYO-EM FOCUSED REFINEMENT MAPS OF TRYPANOSOMA BRUCEI PROCYCLIC FORM 80S RIBOSOME : PARENTAL STRAIN
PDB-8ova: CRYO-EM STRUCTURE OF TRYPANOSOMA BRUCEI PROCYCLIC FORM 80S RIBOSOME : PARENTAL STRAIN
Method: EM (single particle) / Resolution: 2.47 Å

EMDB-17254: CRYO-EM CONSENSUS MAP OF TRYPANOSOMA BRUCEI PROCYCLIC FORM 80S RIBOSOME : TB11CS6H1 SKO
PDB-8ove: CRYO-EM STRUCTURE OF TRYPANOSOMA BRUCEI PROCYCLIC FORM 80S RIBOSOME : TB11CS6H1 snoRNA mutant
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-17255: CRYO-EM FOCUSED REFINEMENT OF TRYPANOSOMA BRUCEI PROCYCLIC FORM 80S RIBOSOME : TB11CS6H1 snoRNA mutant
PDB-8ove: CRYO-EM STRUCTURE OF TRYPANOSOMA BRUCEI PROCYCLIC FORM 80S RIBOSOME : TB11CS6H1 snoRNA mutant
Method: EM (single particle) / Resolution: 2.6 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-NA:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER / Water

Source
  • trypanosoma brucei brucei (eukaryote)
KeywordsRIBOSOME / CRYO-EM / TRYPANOSOMA BRUCEI / 80S RIBOSOME

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