Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: The IRES functions as an RNA-based translation factor

Christian M.T. Spahn; Eric Jan; Anke Mulder; Robert A. Grassucci; Peter Sarnow; Joachim Frank

doi:10.1016/j.cell.2004.08.001

Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: The IRES functions as an RNA-based translation factor

Christian M.T. Spahn
, Eric Jan
, Anke Mulder
, Robert A. Grassucci
, Peter Sarnow
, Joachim Frank

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

224 Scopus citations

Abstract

Internal initiation of protein synthesis in eukaryotes is accomplished by recruitment of ribosomes to structured internal ribosome entry sites (IRESs), which are located in certain viral and cellular messenger RNAs. An IRES element in cricket paralysis virus (CrPV) can directly assemble 80S ribosomes in the absence of canonical initiation factors and initiator tRNA. Here we present cryo-EM structures of the CrPV IRES bound to the human ribosomal 40S subunit and to the 80S ribosome. The CrPV IRES adopts a defined, elongate structure within the ribosomal intersubunit space and forms specific contacts with components of the ribosomal A, P, and E sites. Conformational changes in the ribosome as well as within the IRES itself show that CrPV IRES actively manipulates the ribosome. CrPV-like IRES elements seem to act as RNA-based translation factors.

Original language	English (US)
Pages (from-to)	465-475
Number of pages	11
Journal	Cell
Volume	118
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2004.08.001
State	Published - Aug 20 2004
Externally published	Yes

Funding

Supported in part by HHMI and NIH R037 GM29169, R01 GM55440, and P41 RR01219 (to J.F.); NSF DBI-9987844 (to A.M.); NIH (GM55979) (to P.S); DRG-1630 of the Damon Runyon Cancer Research Foundation (to E.J.); and the VolkswagenStiftung (to C.M.T.S.).

Funders	Funder number
Author National Science Foundation National Science Foundation National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health National Science Foundation National Science Foundation	GM55979, DBI-9987844, DRG-1630
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	R037 GM29169, P41 RR01219
Howard Hughes Medical Institute
National Institute of General Medical Sciences	R01GM055440
Damon Runyon Cancer Research Foundation
Volkswagen Foundation

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2004.08.001

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@article{49b6796b7289427f8e9a8c577f102e81,

title = "Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: The IRES functions as an RNA-based translation factor",

abstract = "Internal initiation of protein synthesis in eukaryotes is accomplished by recruitment of ribosomes to structured internal ribosome entry sites (IRESs), which are located in certain viral and cellular messenger RNAs. An IRES element in cricket paralysis virus (CrPV) can directly assemble 80S ribosomes in the absence of canonical initiation factors and initiator tRNA. Here we present cryo-EM structures of the CrPV IRES bound to the human ribosomal 40S subunit and to the 80S ribosome. The CrPV IRES adopts a defined, elongate structure within the ribosomal intersubunit space and forms specific contacts with components of the ribosomal A, P, and E sites. Conformational changes in the ribosome as well as within the IRES itself show that CrPV IRES actively manipulates the ribosome. CrPV-like IRES elements seem to act as RNA-based translation factors.",

author = "Spahn, \{Christian M.T.\} and Eric Jan and Anke Mulder and Grassucci, \{Robert A.\} and Peter Sarnow and Joachim Frank",

note = "Funding Information: Supported in part by HHMI and NIH R037 GM29169, R01 GM55440, and P41 RR01219 (to J.F.); NSF DBI-9987844 (to A.M.); NIH (GM55979) (to P.S); DRG-1630 of the Damon Runyon Cancer Research Foundation (to E.J.); and the VolkswagenStiftung (to C.M.T.S.). ",

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doi = "10.1016/j.cell.2004.08.001",

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T1 - Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes

T2 - The IRES functions as an RNA-based translation factor

AU - Spahn, Christian M.T.

AU - Jan, Eric

AU - Mulder, Anke

AU - Grassucci, Robert A.

AU - Sarnow, Peter

AU - Frank, Joachim

N1 - Funding Information: Supported in part by HHMI and NIH R037 GM29169, R01 GM55440, and P41 RR01219 (to J.F.); NSF DBI-9987844 (to A.M.); NIH (GM55979) (to P.S); DRG-1630 of the Damon Runyon Cancer Research Foundation (to E.J.); and the VolkswagenStiftung (to C.M.T.S.).

PY - 2004/8/20

Y1 - 2004/8/20

N2 - Internal initiation of protein synthesis in eukaryotes is accomplished by recruitment of ribosomes to structured internal ribosome entry sites (IRESs), which are located in certain viral and cellular messenger RNAs. An IRES element in cricket paralysis virus (CrPV) can directly assemble 80S ribosomes in the absence of canonical initiation factors and initiator tRNA. Here we present cryo-EM structures of the CrPV IRES bound to the human ribosomal 40S subunit and to the 80S ribosome. The CrPV IRES adopts a defined, elongate structure within the ribosomal intersubunit space and forms specific contacts with components of the ribosomal A, P, and E sites. Conformational changes in the ribosome as well as within the IRES itself show that CrPV IRES actively manipulates the ribosome. CrPV-like IRES elements seem to act as RNA-based translation factors.

AB - Internal initiation of protein synthesis in eukaryotes is accomplished by recruitment of ribosomes to structured internal ribosome entry sites (IRESs), which are located in certain viral and cellular messenger RNAs. An IRES element in cricket paralysis virus (CrPV) can directly assemble 80S ribosomes in the absence of canonical initiation factors and initiator tRNA. Here we present cryo-EM structures of the CrPV IRES bound to the human ribosomal 40S subunit and to the 80S ribosome. The CrPV IRES adopts a defined, elongate structure within the ribosomal intersubunit space and forms specific contacts with components of the ribosomal A, P, and E sites. Conformational changes in the ribosome as well as within the IRES itself show that CrPV IRES actively manipulates the ribosome. CrPV-like IRES elements seem to act as RNA-based translation factors.

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AN - SCOPUS:4644247805

SN - 0092-8674

VL - 118

SP - 465

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JO - Cell

JF - Cell

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ER -

Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: The IRES functions as an RNA-based translation factor

Abstract

Funding

ASJC Scopus subject areas

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