Initiation of translation by cricket paralysis virus IRES requires its translocation in the ribosome

Israel S. Fernández; Xiao Chen Bai; Garib Murshudov; Sjors H W Scheres; V. Ramakrishnan

doi:10.1016/j.cell.2014.04.015

Initiation of translation by cricket paralysis virus IRES requires its translocation in the ribosome

Israel S. Fernández, Xiao Chen Bai, Garib Murshudov, Sjors H W Scheres, V. Ramakrishnan

Research output: Contribution to journal › Article › peer-review

170 Scopus citations

Abstract

The cricket paralysis virus internal ribosome entry site (CrPV-IRES) is a folded structure in a viral mRNA that allows initiation of translation in the absence of any host initiation factors. By using recent advances in single-particle electron cryomicroscopy, we have solved the structure of CrPV-IRES bound to the ribosome of the yeast Kluyveromyces lactis in both the canonical and rotated states at overall resolutions of 3.7 and 3.8 Å, respectively. In both states, the pseudoknot PKI of the CrPV-IRES mimics a tRNA/mRNA interaction in the decoding center of the A site of the 40S ribosomal subunit. The structure and accompanying factor-binding data show that CrPV-IRES binding mimics a pretranslocation rather than initiation state of the ribosome. Translocation of the IRES by elongation factor 2 (eEF2) is required to bring the first codon of the mRNA into the A site and to allow the start of translation.

Original language	English (US)
Pages (from-to)	823-831
Number of pages	9
Journal	Cell
Volume	157
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2014.04.015
State	Published - May 8 2014

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2014.04.015

Cite this

@article{54ee6344a4804ab6b6b23880b95c74a4,

title = "Initiation of translation by cricket paralysis virus IRES requires its translocation in the ribosome",

abstract = "The cricket paralysis virus internal ribosome entry site (CrPV-IRES) is a folded structure in a viral mRNA that allows initiation of translation in the absence of any host initiation factors. By using recent advances in single-particle electron cryomicroscopy, we have solved the structure of CrPV-IRES bound to the ribosome of the yeast Kluyveromyces lactis in both the canonical and rotated states at overall resolutions of 3.7 and 3.8 {\AA}, respectively. In both states, the pseudoknot PKI of the CrPV-IRES mimics a tRNA/mRNA interaction in the decoding center of the A site of the 40S ribosomal subunit. The structure and accompanying factor-binding data show that CrPV-IRES binding mimics a pretranslocation rather than initiation state of the ribosome. Translocation of the IRES by elongation factor 2 (eEF2) is required to bring the first codon of the mRNA into the A site and to allow the start of translation.",

author = "Fern{\'a}ndez, {Israel S.} and Bai, {Xiao Chen} and Garib Murshudov and Scheres, {Sjors H W} and V. Ramakrishnan",

note = "Funding Information: We are grateful to Shaoxia Chen for technical support with cryo-EM, Greg McMullan for help in movie data acquisition, Toby Darling and Jake Grimmett for help with computing, David Tourigny and Alan Brown for discussions, Ann C. Kelley for advice and help in RNA production, and Wojciech Galej and Andrew Newman for advice in yeast protein expression. X.-C.B. is supported by an EU FP7 Marie Curie postdoctoral fellowship. This work was funded by grants from the UK Medical Research Council (MC_U105184332 to V.R. and MC_UP_A025_1013 to SHWS) and a Wellcome Trust Senior Investigator award (WT096570), the Agouron Institute, and the Jeantet Foundation (V.R.). ",

year = "2014",

month = may,

day = "8",

doi = "10.1016/j.cell.2014.04.015",

language = "English (US)",

volume = "157",

pages = "823--831",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - Initiation of translation by cricket paralysis virus IRES requires its translocation in the ribosome

AU - Fernández, Israel S.

AU - Bai, Xiao Chen

AU - Murshudov, Garib

AU - Scheres, Sjors H W

AU - Ramakrishnan, V.

N1 - Funding Information: We are grateful to Shaoxia Chen for technical support with cryo-EM, Greg McMullan for help in movie data acquisition, Toby Darling and Jake Grimmett for help with computing, David Tourigny and Alan Brown for discussions, Ann C. Kelley for advice and help in RNA production, and Wojciech Galej and Andrew Newman for advice in yeast protein expression. X.-C.B. is supported by an EU FP7 Marie Curie postdoctoral fellowship. This work was funded by grants from the UK Medical Research Council (MC_U105184332 to V.R. and MC_UP_A025_1013 to SHWS) and a Wellcome Trust Senior Investigator award (WT096570), the Agouron Institute, and the Jeantet Foundation (V.R.).

PY - 2014/5/8

Y1 - 2014/5/8

N2 - The cricket paralysis virus internal ribosome entry site (CrPV-IRES) is a folded structure in a viral mRNA that allows initiation of translation in the absence of any host initiation factors. By using recent advances in single-particle electron cryomicroscopy, we have solved the structure of CrPV-IRES bound to the ribosome of the yeast Kluyveromyces lactis in both the canonical and rotated states at overall resolutions of 3.7 and 3.8 Å, respectively. In both states, the pseudoknot PKI of the CrPV-IRES mimics a tRNA/mRNA interaction in the decoding center of the A site of the 40S ribosomal subunit. The structure and accompanying factor-binding data show that CrPV-IRES binding mimics a pretranslocation rather than initiation state of the ribosome. Translocation of the IRES by elongation factor 2 (eEF2) is required to bring the first codon of the mRNA into the A site and to allow the start of translation.

AB - The cricket paralysis virus internal ribosome entry site (CrPV-IRES) is a folded structure in a viral mRNA that allows initiation of translation in the absence of any host initiation factors. By using recent advances in single-particle electron cryomicroscopy, we have solved the structure of CrPV-IRES bound to the ribosome of the yeast Kluyveromyces lactis in both the canonical and rotated states at overall resolutions of 3.7 and 3.8 Å, respectively. In both states, the pseudoknot PKI of the CrPV-IRES mimics a tRNA/mRNA interaction in the decoding center of the A site of the 40S ribosomal subunit. The structure and accompanying factor-binding data show that CrPV-IRES binding mimics a pretranslocation rather than initiation state of the ribosome. Translocation of the IRES by elongation factor 2 (eEF2) is required to bring the first codon of the mRNA into the A site and to allow the start of translation.

UR - http://www.scopus.com/inward/record.url?scp=84900435661&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84900435661&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2014.04.015

DO - 10.1016/j.cell.2014.04.015

M3 - Article

C2 - 24792965

AN - SCOPUS:84900435661

SN - 0092-8674

VL - 157

SP - 823

EP - 831

JO - Cell

JF - Cell

IS - 4

ER -

Initiation of translation by cricket paralysis virus IRES requires its translocation in the ribosome

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this