| Autor: |
Acosta‐Reyes, Francisco, Neupane, Ritam, Frank, Joachim, Fernández, Israel S |
| Předmět: |
|
| Zdroj: |
EMBO Journal; 11/4/2019, Vol. 38 Issue 21, pN.PAG-N.PAG, 1p, 7 Diagrams |
| Abstrakt: |
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. Synopsis: Israeli acute paralysis virus (IAPV) affects honeybee hives worldwide and acts by hijacking the host ribosome for viral protein production through a non‐coding RNA sequences termed IRESs. Cryo‐EM studies now reveal how the IRES captures host ribosomes by mimicking tRNAs in hybrid configurations to bypass the initiation step, jumpstarting translation directly to the elongation phase. Cryo‐EM reconstructions of the IAPV IRES in complex with eukaryotic ribosomes reveal molecular details of ribosome hijacking.Hybrid‐tRNA mimicry allows the IAPV‐IRES to divert ribosomes from canonical pathways thereby redirecting them towards the production of viral proteins.The IAPV IRES restricts the intrinsic dynamics of the 40S subunit's head to a configuration compatible with large subunit recruitment, and blocks binding sites for canonical initiation factors. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Plný text