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TitleA complex IRES at the 5'-UTR of a viral mRNA assembles a functional 48S complex via an uAUG intermediate.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateApr 14, 2020
AuthorsRitam Neupane / Vera P Pisareva / Carlos F Rodriguez / Andrey V Pisarev / Israel S Fernández /
PubMed AbstractTaking control of the cellular apparatus for protein production is a requirement for virus progression. To ensure this control, diverse strategies of cellular mimicry and/or ribosome hijacking have ...Taking control of the cellular apparatus for protein production is a requirement for virus progression. To ensure this control, diverse strategies of cellular mimicry and/or ribosome hijacking have evolved. The initiation stage of translation is especially targeted as it involves multiple steps and the engagement of numerous initiation factors. The use of structured RNA sequences, called nternal ibosomal ntry ites (IRES), in viral RNAs is a widespread strategy for the exploitation of eukaryotic initiation. Using a combination of electron cryo-microscopy (cryo-EM) and reconstituted translation initiation assays with native components, we characterized how a novel IRES at the 5'-UTR of a viral RNA assembles a functional initiation complex via an uAUG intermediate. The IRES features a novel extended, multi-domain architecture, that circles the 40S head. The structures and accompanying functional data illustrate the importance of 5'-UTR regions in translation regulation and underline the relevance of the untapped diversity of viral IRESs.
External linksElife / PubMed:32286223 / PubMed Central
MethodsEM (single particle)
Resolution2.79 - 3.47 Å
Structure data

EMDB-21529, PDB-6w2s:
Structure of the Cricket Paralysis Virus 5-UTR IRES (CrPV 5-UTR-IRES) bound to the small ribosomal subunit in the open state (Class 1)
Method: EM (single particle) / Resolution: 3.47 Å

EMDB-21530, PDB-6w2t:
Structure of the Cricket Paralysis Virus 5-UTR IRES (CrPV 5-UTR-IRES) bound to the small ribosomal subunit in the closed state (Class 2)
Method: EM (single particle) / Resolution: 3.36 Å

EMDB-21531:
Head masked 3D refined density of the Cricket Paralysis Virus 5-UTR IRES (CrPV 5-UTR-IRES) bound to the small ribosomal subunit used to build the 5-UTR IRES model
Method: EM (single particle) / Resolution: 2.79 Å

Chemicals

ChemComp-MG:
MAGNESIUM ION / Magnesium

ChemComp-ZN:
ZINC ION / Zinc

Source
  • oryctolagus cuniculus (rabbit)
  • cricket paralysis virus
  • Rabbit (rabbit)
Keywords5' Untranslated Regions / Animals / Cryoelectron Microscopy / Dicistroviridae / Eukaryotic Initiation Factor-3 / Humans / Internal Ribosome Entry Sites / Models, Molecular / Protein Biosynthesis / Protein Conformation / RNA, Messenger / RNA, Viral / Ribosome Subunits / Ribosome/TRANSLATION / CrPV 5'-UTR IRES / Internal ribosome entry site / RIBOSOME / Ribosome-TRANSLATION complex

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