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TitleThe Israeli acute paralysis virus IRES captures host ribosomes by mimicking a ribosomal state with hybrid tRNAs.
Journal, issue, pagesEMBO J, Vol. 38, Issue 21, Page e102226, Year 2019
Publish dateOct 4, 2019
AuthorsFrancisco Acosta-Reyes / Ritam Neupane / Joachim Frank / Israel S Fernández /
PubMed AbstractColony collapse disorder (CCD) is a multi-faceted syndrome decimating bee populations worldwide, and a group of viruses of the widely distributed Dicistroviridae family have been identified as a ...Colony collapse disorder (CCD) is a multi-faceted syndrome decimating bee populations worldwide, and a group of viruses of the widely distributed Dicistroviridae family have been identified as a causing agent of CCD. This family of viruses employs non-coding RNA sequences, called internal ribosomal entry sites (IRESs), to precisely exploit the host machinery for viral protein production. Using single-particle cryo-electron microscopy (cryo-EM), we have characterized how the IRES of Israeli acute paralysis virus (IAPV) intergenic region captures and redirects translating ribosomes toward viral RNA messages. We reconstituted two in vitro reactions targeting a pre-translocation and a post-translocation state of the IAPV-IRES in the ribosome, allowing us to identify six structures using image processing classification methods. From these, we reconstructed the trajectory of IAPV-IRES from the early small subunit recruitment to the final post-translocated state in the ribosome. An early commitment of IRES/ribosome complexes for global pre-translocation mimicry explains the high efficiency observed for this IRES. Efforts directed toward fighting CCD by targeting the IAPV-IRES using RNA-interference technology are underway, and the structural framework presented here may assist in further refining these approaches.
External linksEMBO J / PubMed:31609474 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 3.2 Å
Structure data

EMDB-20248, PDB-6p4g:
Structure of a mammalian small ribosomal subunit in complex with the Israeli Acute Paralysis Virus IRES (Class 1)
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-20249, PDB-6p4h:
Structure of a mammalian small ribosomal subunit in complex with the Israeli Acute Paralysis Virus IRES (Class 2)
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-20255, PDB-6p5i:
Structure of a mammalian 80S ribosome in complex with the Israeli Acute Paralysis Virus IRES (Class 1)
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-20256, PDB-6p5j:
Structure of a mammalian 80S ribosome in complex with the Israeli Acute Paralysis Virus IRES (Class 2)
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-20257, PDB-6p5k:
Structure of a mammalian 80S ribosome in complex with the Israeli Acute Paralysis Virus IRES (Class 3)
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-20258, PDB-6p5n:
Structure of a mammalian 80S ribosome in complex with a single translocated Israeli Acute Paralysis Virus IRES and eRF1
Method: EM (single particle) / Resolution: 3.2 Å

Source
  • israeli acute paralysis virus
  • oryctolagus cuniculus (rabbit)
  • Rabbit (rabbit)
  • homo sapiens (human)
KeywordsRIBOSOME / Israeli Acute Paralysis Virus IRES / IAPV / 40S / small ribosomal subunit / Israeli Acute Paralysis Virus / Internal Ribosome Entry Site / IRES / Large Ribosomal Subunit / 60S / 80S / ribosomes / eukaryotic release factor 1 / eRF1

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