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Updated: Jun 7, 2025

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
Published on: May 10, 2018
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.
None:
The CCR4-NOT complex is a major regulator of eukaryotic messenger RNA (mRNA) stability. Slow decoding during translation promotes association of CCR4-NOT with ribosomes, accelerating mRNA degradation. We applied selective ribosome profiling to further investigate the determinants of CCR4-NOT recruitment to ribosomes in mammalian cells. This revealed that specific arginine codons in the P-site are strong signals for ribosomal recruitment of human CNOT3, a CCR4-NOT subunit. Cryo-electron microscopy and transfer RNA (tRNA) mutagenesis demonstrated that the D-arms of select arginine tRNAs interact with CNOT3 and promote its recruitment whereas other tRNA D-arms sterically clash with CNOT3. These effects link codon content to mRNA stability. Thus, in addition to their canonical decoding function, tRNAs directly engage regulatory complexes during translation, a mechanism we term P-site tRNA-mediated mRNA decay.
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