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Videos de Conceptos Relacionados

Translation01:31

Translation

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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...
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Translation01:31

Translation

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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...
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Initiation of Translation02:33

Initiation of Translation

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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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Termination of Translation01:44

Termination of Translation

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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...
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Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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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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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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La reprogramación de la traducción específica del códon promueve la resistencia a la terapia dirigida

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

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

Nature
|June 22, 2018
PubMed
Resumen

Las enzimas de modificación del tRNA de oscilación son cruciales para la supervivencia de las células de melanoma y la resistencia a los medicamentos. La inhibición de estas enzimas, junto con la señalización de MAPK, ofrece una estrategia terapéutica prometedora para el melanoma.

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Área de la Ciencia:

  • Biología molecular
  • En el campo de la oncología
  • La bioquímica

Sus antecedentes:

  • La reprogramación de la traducción del ARNm está implicada en el desarrollo del cáncer y la resistencia a los medicamentos.
  • Los mecanismos moleculares precisos que subyacen a la reprogramación de la traducción siguen siendo en gran medida desconocidos.
  • Las modificaciones del tRNA de oscilación son esenciales para la decodificación precisa del codón durante la síntesis de proteínas.

Objetivo del estudio:

  • Investigar el papel de las enzimas modificadoras del tRNA de la uridina 34 (U34) en el melanoma impulsado por BRAF V600E.
  • Explorar la participación de las enzimas U34 en la resistencia terapéutica a los inhibidores de la MAPK.
  • Para aclarar el vínculo mecánico entre las enzimas U34, la síntesis de proteínas y la supervivencia de las células de melanoma.

Principales métodos:

  • Análisis de la expresión de la enzima U34 en los modelos de melanoma BRAF V600E.
  • Evaluación de la viabilidad celular tras la inhibición simultánea de la señalización de MAPK y de las enzimas U34 (ELP3, CTU1, CTU2).
  • Investigación de la activación de la vía PI3K y su efecto sobre la expresión de la enzima U34.
  • Examen de la regulación mediada por la enzima U34 de la traducción del ARNm HIF1A y de los niveles de proteína HIF1α.

Principales resultados:

  • Las células de melanoma BRAF V600E muestran dependencia de las enzimas U34 para su supervivencia.
  • La inhibición combinada de la señalización MAPK y de las enzimas U34 demuestra una citotoxicidad sinérgica.
  • La activación de la vía PI3K, un mecanismo de resistencia, aumenta significativamente la expresión de la enzima U34.
  • Las enzimas U34 promueven la glucólisis en el melanoma mediante la regulación de la traducción de HIF1A y el mantenimiento de los niveles de proteína HIF1α.

Conclusiones:

  • Las enzimas U34 son mediadores críticos de la recombinación de la síntesis de proteínas en el melanoma BRAF V600E.
  • Dirigirse a las enzimas U34, en combinación con inhibidores de MAPK, presenta una estrategia terapéutica potencial para el melanoma.
  • Los altos niveles de enzimas U34 y HIF1α están asociados con la resistencia adquirida a la terapia anti-BRAF, destacando su papel en la promoción de la supervivencia celular del melanoma y la resistencia terapéutica.