EMD-28643
Hypopseudouridylated yeast 80S bound with Taura syndrome virus (TSV) internal ribosome entry site (IRES), Structure II
EMD-28643
Single-particle2.45 Å
Deposition: 22/10/2022
Map released: 06/09/2023
Last modified: 06/09/2023
Sample Organism:
Saccharomyces cerevisiae,
Taura syndrome virus
Sample: Hypopseudouridylated ribosome with TSV IRES, eEF2 and GDP
Fitted models: 8ewc (Avg. Q-score: 0.532)
Raw data: EMPIAR-12070
Deposition Authors: Zhao Y , Rai J , Li H
Sample: Hypopseudouridylated ribosome with TSV IRES, eEF2 and GDP
Fitted models: 8ewc (Avg. Q-score: 0.532)
Raw data: EMPIAR-12070
Deposition Authors: Zhao Y , Rai J , Li H
Regulation of translation by ribosomal RNA pseudouridylation.
Abstract:
Pseudouridine is enriched in ribosomal, spliceosomal, transfer, and messenger RNA and thus integral to the central dogma. The chemical basis for how pseudouridine affects the molecular apparatus such as ribosome, however, remains elusive owing to the lack of structures without this natural modification. Here, we studied the translation of a hypopseudouridylated ribosome initiated by the internal ribosome entry site (IRES) elements. We analyzed eight cryo-electron microscopy structures of the ribosome bound with the Taura syndrome virus IRES in multiple functional states. We found widespread loss of pseudouridine-mediated interactions through water and long-range base pairings. In the presence of the translocase, eukaryotic elongation factor 2, and guanosine 5'-triphosphate hydrolysis, the hypopseudouridylated ribosome favors a rare unconducive conformation for decoding that is partially recouped in the ribosome population that remains modified at the P-site uridine. The structural principles learned establish the link between functional defects and modification loss and are likely applicable to other pseudouridine-associated processes.
Pseudouridine is enriched in ribosomal, spliceosomal, transfer, and messenger RNA and thus integral to the central dogma. The chemical basis for how pseudouridine affects the molecular apparatus such as ribosome, however, remains elusive owing to the lack of structures without this natural modification. Here, we studied the translation of a hypopseudouridylated ribosome initiated by the internal ribosome entry site (IRES) elements. We analyzed eight cryo-electron microscopy structures of the ribosome bound with the Taura syndrome virus IRES in multiple functional states. We found widespread loss of pseudouridine-mediated interactions through water and long-range base pairings. In the presence of the translocase, eukaryotic elongation factor 2, and guanosine 5'-triphosphate hydrolysis, the hypopseudouridylated ribosome favors a rare unconducive conformation for decoding that is partially recouped in the ribosome population that remains modified at the P-site uridine. The structural principles learned establish the link between functional defects and modification loss and are likely applicable to other pseudouridine-associated processes.