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Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes

Xiaoqiang Zhu1, Victor Emmanuel Cruz2, He Zhang3,4

  • 1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Science (New York, N.Y.)
|November 21, 2024
PubMed

Insights

Specific arginine codons recruit the CCR4-NOT complex to ribosomes, influencing messenger RNA (mRNA) stability. Transfer RNAs (tRNAs) directly engage regulatory complexes during translation, a process termed P-site tRNA-mediated mRNA decay.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Biochemistry

Background:

  • The CCR4-NOT complex is a key regulator of eukaryotic messenger RNA (mRNA) stability.
  • Translation speed influences CCR4-NOT complex association with ribosomes, affecting mRNA degradation rates.

Purpose of the Study:

  • To investigate the specific determinants of CCR4-NOT complex recruitment to ribosomes in mammalian cells.
  • To elucidate the role of codon sequences and transfer RNAs (tRNAs) in this recruitment process.

Main Methods:

  • Selective ribosome profiling was employed to analyze ribosome-associated factors.
  • Cryo-electron microscopy and transfer RNA (tRNA) mutagenesis were used to study molecular interactions.

Main Results:

  • Specific arginine codons in the ribosomal P-site act as signals for recruiting the CNOT3 subunit of the CCR4-NOT complex.
  • The D-arms of certain arginine tRNAs interact with CNOT3, promoting its recruitment.
  • Other tRNA D-arms sterically hinder CNOT3 binding, demonstrating a direct link between codon content and mRNA stability.

Conclusions:

  • Transfer RNAs (tRNAs) directly engage with regulatory complexes like CCR4-NOT during translation.
  • This interaction, termed P-site tRNA-mediated mRNA decay, links codon composition to mRNA stability beyond canonical decoding functions.

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