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Related Concept Videos

Initiation of Translation02:33

Initiation of Translation

32.1K
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...
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Improving Translational Accuracy02:07

Improving Translational Accuracy

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Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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Leaky Scanning02:28

Leaky Scanning

5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Termination of Translation01:44

Termination of Translation

25.3K
The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
25.3K
Regulated mRNA Transport02:22

Regulated mRNA Transport

6.3K
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...
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Post-translational Translocation of Proteins to the RER01:27

Post-translational Translocation of Proteins to the RER

5.7K
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
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Related Experiment Video

Updated: Jun 17, 2025

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

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eIF4E-independent translation is largely eIF3d-dependent.

Mykola Roiuk1,2,3, Marilena Neff1,2,3, Aurelio A Teleman4,5,6

  • 1German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.

Nature Communications
|August 6, 2024
PubMed
Summary

Cells can translate messenger RNAs (mRNAs) independently of the eukaryotic initiation factor 4E1 (eIF4E1) under stress. This alternative pathway utilizes eukaryotic initiation factor 3d (eIF3d) to facilitate protein synthesis when eIF4E1 is inactivated.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Canonical translation initiation relies on cap recognition by eukaryotic initiation factor 4E1 (eIF4E1).
  • Cellular stresses like hypoxia and nutrient deprivation inactivate mTORC1, leading to eIF4E1 inactivation.
  • Understanding mRNA translation under stress is crucial, particularly in contexts like tumor cells.

Purpose of the Study:

  • To investigate mechanisms of mRNA translation independent of eIF4E1 under stress conditions.
  • To identify specific mRNAs and factors involved in eIF4E1-independent translation.

Main Methods:

  • Blocking eIF4E1 activity using a constitutively active 4E-binding protein (4E-BP).
  • Employing ribosome profiling to analyze mRNA translation efficiency.
  • Investigating protein-RNA interactions using cap-binding assays.

Main Results:

  • A subset of mRNAs remains efficiently translated when eIF4E1 is inactive.
  • These mRNAs preferentially release eIF4E1 and bind to eukaryotic initiation factor 3d (eIF3d) via its cap-binding pocket.
  • eIF3d facilitates mRNA translation in an eIF4E1-independent manner.

Conclusions:

  • eIF3d-dependent translation is a significant mechanism for mRNA translation under stress.
  • This pathway provides a crucial alternative for protein synthesis when canonical initiation is compromised.