Dual tRNA mimicry in the Cricket Paralysis Virus IRES uncovers an unexpected similarity with the Hepatitis C Virus IRES

Co-opting the cellular machinery for protein production is a compulsory requirement for viruses. The Cricket Paralysis Virus employs an Internal Ribosomal Entry Site (CrPV-IRES) to express its structural genes in the late stage of infection. Ribosome hijacking is achieved by a sophisticated use of m...

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Main Authors: Vera P Pisareva, Andrey V Pisarev, Israel S Fernández
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-06-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/34062
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author Vera P Pisareva
Andrey V Pisarev
Israel S Fernández
author_facet Vera P Pisareva
Andrey V Pisarev
Israel S Fernández
author_sort Vera P Pisareva
collection DOAJ
description Co-opting the cellular machinery for protein production is a compulsory requirement for viruses. The Cricket Paralysis Virus employs an Internal Ribosomal Entry Site (CrPV-IRES) to express its structural genes in the late stage of infection. Ribosome hijacking is achieved by a sophisticated use of molecular mimicry to tRNA and mRNA, employed to manipulate intrinsically dynamic components of the ribosome. Binding and translocation through the ribosome is required for this IRES to initiate translation. We report two structures, solved by single particle electron cryo-microscopy (cryoEM), of a double translocated CrPV-IRES with aminoacyl-tRNA in the peptidyl site (P site) of the ribosome. CrPV-IRES adopts a previously unseen conformation, mimicking the acceptor stem of a canonical E site tRNA. The structures suggest a mechanism for the positioning of the first aminoacyl-tRNA shared with the distantly related Hepatitis C Virus IRES.
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spelling doaj.art-e5896752877b4aba8d8b053bf2c1b78b2022-12-22T04:29:21ZengeLife Sciences Publications LtdeLife2050-084X2018-06-01710.7554/eLife.34062Dual tRNA mimicry in the Cricket Paralysis Virus IRES uncovers an unexpected similarity with the Hepatitis C Virus IRESVera P Pisareva0Andrey V Pisarev1Israel S Fernández2https://orcid.org/0000-0001-7218-1603Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, United StatesDepartment of Cell Biology, SUNY Downstate Medical Center, Brooklyn, United StatesDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, United StatesCo-opting the cellular machinery for protein production is a compulsory requirement for viruses. The Cricket Paralysis Virus employs an Internal Ribosomal Entry Site (CrPV-IRES) to express its structural genes in the late stage of infection. Ribosome hijacking is achieved by a sophisticated use of molecular mimicry to tRNA and mRNA, employed to manipulate intrinsically dynamic components of the ribosome. Binding and translocation through the ribosome is required for this IRES to initiate translation. We report two structures, solved by single particle electron cryo-microscopy (cryoEM), of a double translocated CrPV-IRES with aminoacyl-tRNA in the peptidyl site (P site) of the ribosome. CrPV-IRES adopts a previously unseen conformation, mimicking the acceptor stem of a canonical E site tRNA. The structures suggest a mechanism for the positioning of the first aminoacyl-tRNA shared with the distantly related Hepatitis C Virus IRES.https://elifesciences.org/articles/34062rabbitreticulocyteribosome
spellingShingle Vera P Pisareva
Andrey V Pisarev
Israel S Fernández
Dual tRNA mimicry in the Cricket Paralysis Virus IRES uncovers an unexpected similarity with the Hepatitis C Virus IRES
eLife
rabbit
reticulocyte
ribosome
title Dual tRNA mimicry in the Cricket Paralysis Virus IRES uncovers an unexpected similarity with the Hepatitis C Virus IRES
title_full Dual tRNA mimicry in the Cricket Paralysis Virus IRES uncovers an unexpected similarity with the Hepatitis C Virus IRES
title_fullStr Dual tRNA mimicry in the Cricket Paralysis Virus IRES uncovers an unexpected similarity with the Hepatitis C Virus IRES
title_full_unstemmed Dual tRNA mimicry in the Cricket Paralysis Virus IRES uncovers an unexpected similarity with the Hepatitis C Virus IRES
title_short Dual tRNA mimicry in the Cricket Paralysis Virus IRES uncovers an unexpected similarity with the Hepatitis C Virus IRES
title_sort dual trna mimicry in the cricket paralysis virus ires uncovers an unexpected similarity with the hepatitis c virus ires
topic rabbit
reticulocyte
ribosome
url https://elifesciences.org/articles/34062
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AT andreyvpisarev dualtrnamimicryinthecricketparalysisvirusiresuncoversanunexpectedsimilaritywiththehepatitiscvirusires
AT israelsfernandez dualtrnamimicryinthecricketparalysisvirusiresuncoversanunexpectedsimilaritywiththehepatitiscvirusires