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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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The Spindle Assembly Checkpoint02:19

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The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
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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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The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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El estancamiento elongacional activa el control de calidad asociado al mitoribosoma

Nirupa Desai1, Hanting Yang1, Viswanathan Chandrasekaran1

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Los investigadores descubrieron una vía de control de calidad en los ribosomas mitocondriales humanos (mitoribosomas) que rescata la síntesis de proteínas estancada. Las proteínas clave expulsan las cadenas nacientes y el ARNt, asegurando la función adecuada de los complejos de fosforilación oxidativa.

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Área de la Ciencia:

  • Biología celular
  • Biología molecular
  • La bioquímica

Sus antecedentes:

  • El ribosoma mitocondrial humano (mitoribosoma) es crucial para sintetizar 13 subunidades esenciales de fosforilación oxidativa (OXPHOS).
  • La función del mitoribosoma es vital para la producción de energía celular.

Objetivo del estudio:

  • Descubrir y caracterizar una vía de control de calidad para los mitoribosomas estancados.
  • Para aclarar los mecanismos estructurales del rescate de ribosomas.

Principales métodos:

  • Microscopía cryoelectrónica (cryo-EM) con una resolución de entre 3,1 y 4,4 angstroms.
  • Análisis bioquímico de las interacciones proteína-ARN y proteína-proteína.

Principales resultados:

  • Se determinaron las estructuras de las subunidades grandes del mitoribosoma atrapadas durante el rescate del ribosoma.
  • Identificó C12orf65 (mtRF-R) y C6orf203 (MTRES1) como factores clave en la eyección de las cadenas nacientes y el ARNt peptídico.
  • Reclutamiento observado de factores de la biogénesis del mitoribosoma en los productos intermedios de control de calidad.
  • Estructuras proporcionadas de mitoribosomas alargados con factores de alargamiento y Oxa1L.

Conclusiones:

  • Una nueva vía de control de calidad asociada al mitoribosoma rescata la traducción estancada durante el alargamiento.
  • mtRF-R y MTRES1 juegan un papel crítico en el rescate del mitoribosoma.
  • Los factores de biogénesis del mitoribosoma tienen funciones adicionales en el control de calidad.