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Related Concept Videos

Translation01:31

Translation

157.1K
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
157.1K
Translation01:31

Translation

17.9K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
17.9K
Initiation of Translation02:33

Initiation of Translation

39.1K
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...
39.1K
Improving Translational Accuracy02:07

Improving Translational Accuracy

15.0K
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...
15.0K
Termination of Translation01:44

Termination of Translation

27.8K
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...
27.8K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

8.9K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
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Related Experiment Video

Updated: Feb 8, 2026

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
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Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

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Codon-specific translation reprogramming promotes resistance to targeted therapy.

Francesca Rapino1,2, Sylvain Delaunay1,2, Florian Rambow3,4

  • 1Laboratory of Cancer Signaling, University of Liège, Liège, Belgium.

Nature
|June 22, 2018
PubMed
Summary

Wobble tRNA modification enzymes are crucial for melanoma cell survival and drug resistance. Inhibiting these enzymes, alongside MAPK signaling, offers a promising therapeutic strategy for melanoma.

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Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • mRNA translation reprogramming is implicated in cancer development and drug resistance.
  • The precise molecular mechanisms underlying translation reprogramming remain largely unknown.
  • Wobble tRNA modifications are essential for accurate codon decoding during protein synthesis.

Purpose of the Study:

  • To investigate the role of wobble uridine 34 (U34) tRNA modifying enzymes in BRAF V600E-driven melanoma.
  • To explore the involvement of U34 enzymes in therapeutic resistance to MAPK inhibitors.
  • To elucidate the mechanistic link between U34 enzymes, protein synthesis, and melanoma cell survival.

Main Methods:

  • Analysis of U34 enzyme expression in BRAF V600E melanoma models.
  • Assessment of cell viability upon concurrent inhibition of MAPK signaling and U34 enzymes (ELP3, CTU1, CTU2).
  • Investigation of PI3K pathway activation and its effect on U34 enzyme expression.
  • Examination of U34 enzyme-mediated regulation of HIF1A mRNA translation and HIF1α protein levels.

Main Results:

  • BRAF V600E melanoma cells exhibit dependence on U34 enzymes for survival.
  • Combined inhibition of MAPK signaling and U34 enzymes demonstrates synergistic cytotoxicity.
  • PI3K pathway activation, a resistance mechanism, significantly upregulates U34 enzyme expression.
  • U34 enzymes promote glycolysis in melanoma by regulating HIF1A translation and maintaining HIF1α protein levels.

Conclusions:

  • U34 enzymes are critical mediators of protein synthesis rewiring in BRAF V600E melanoma.
  • Targeting U34 enzymes, in combination with MAPK inhibitors, presents a potential therapeutic strategy for melanoma.
  • High levels of U34 enzymes and HIF1α are associated with acquired resistance to anti-BRAF therapy, highlighting their role in promoting melanoma cell survival and therapeutic resistance.