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Related Concept Videos

Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
Initiation of Translation02:33

Initiation of Translation

Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
Regulated mRNA Transport02:22

Regulated mRNA Transport

In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing specific...
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
Initiation of Translation02:33

Initiation of Translation

Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
Regulated mRNA Transport02:22

Regulated mRNA Transport

In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing specific...

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Xenopus laevis as a Model to Identify Translation Impairment
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Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E.

John D Gross1, Nathan J Moerke, Tobias von der Haar

  • 1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

Cell
|December 17, 2003
PubMed
Summary

The eukaryotic initiation factor 4G (eIF4G) binds eIF4E and mRNA cap, forming a molecular bracelet. This structure enhances translation initiation and is vital for cell growth.

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Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions
10:40

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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Gene Expression Regulation

Background:

  • Eukaryotic initiation factor 4G (eIF4G) is central to translation initiation, controlling gene expression.
  • eIF4G interacts with eIF3 and the eIF4E/cap-mRNA complex to facilitate ribosome loading onto mRNA.
  • Cap-dependent translation is a critical process for protein synthesis.

Purpose of the Study:

  • To determine the solution structure of the complex between yeast eIF4E/cap and a fragment of eIF4G (393-490).
  • To elucidate the mechanism by which eIF4G and eIF4E interact to regulate translation initiation.

Main Methods:

  • Solution structure determination of the eIF4E/cap and eIF4G (393-490) complex.
  • Analysis of the structural consequences of binding on both proteins.

Main Results:

  • Binding of eIF4G (393-490) to eIF4E/cap induces a coupled folding transition.
  • A stable 'molecular bracelet' is formed, with eIF4G (393-490) forming a helical ring around the N-terminus of eIF4E.
  • This cofolding allosterically enhances eIF4E's association with the mRNA cap.

Conclusions:

  • The eIF4G-eIF4E interaction and resulting structure are crucial for optimal cell growth and polysome distribution.
  • The stable messenger ribonucleoprotein (mRNP) complex facilitates multiple rounds of ribosomal loading, impacting protein synthesis rates.