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-Structure paper
Title | Regulation of translation by ribosomal RNA pseudouridylation. |
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Journal, issue, pages | Sci Adv, Vol. 9, Issue 33, Page eadg8190, Year 2023 |
Publish date | Aug 18, 2023 |
Authors | Yu Zhao / Jay Rai / Hong Li / |
PubMed 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 ...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. |
External links | Sci Adv / PubMed:37595043 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.2 - 2.87 Å |
Structure data | EMDB-28610, PDB-8eub: EMDB-28632, PDB-8evp: EMDB-28633, PDB-8evq: EMDB-28634, PDB-8evr: EMDB-28635, PDB-8evs: EMDB-28636, PDB-8evt: EMDB-28642, PDB-8ewb: EMDB-28643, PDB-8ewc: |
Chemicals | ChemComp-MG: ChemComp-ZN: ChemComp-GDP: ChemComp-SO1: ChemComp-W9C: |
Source |
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Keywords | RIBOSOME / rRNA pseudouridylation / IRES initiation / confomation / eEF2. / eEF2 / Hypopseudouridylation / IRES-dependent translation / RNA modification / Ribosome/RNA / Ribosome-RNA complex / pseudouridine / IRES |