Cryo-EM Visualization of a Viral Internal Ribosome Entry Site Bound to Human Ribosomes: The IRES Functions as an RNA-Based Translation Factor

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 ribosome...

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Veröffentlicht in:Cell 2004-08, Vol.118 (4), p.465-475
Hauptverfasser: Spahn, Christian M.T., Jan, Eric, Mulder, Anke, Grassucci, Robert A., Sarnow, Peter, Frank, Joachim
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container_end_page 475
container_issue 4
container_start_page 465
container_title Cell
container_volume 118
creator Spahn, Christian M.T.
Jan, Eric
Mulder, Anke
Grassucci, Robert A.
Sarnow, Peter
Frank, Joachim
description 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.
doi_str_mv 10.1016/j.cell.2004.08.001
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subjects Conserved Sequence
Cricket paralysis virus
Cryoelectron Microscopy - methods
Escherichia coli - metabolism
HeLa Cells
Humans
Models, Molecular
Protein Binding
Protein Biosynthesis
Protein Conformation
Ribosomes - chemistry
Ribosomes - metabolism
RNA, Messenger - metabolism
RNA, Transfer - metabolism
RNA, Viral - metabolism
title Cryo-EM Visualization of a Viral Internal Ribosome Entry Site Bound to Human Ribosomes: The IRES Functions as an RNA-Based Translation Factor
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