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| Title | Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes. |
|---|---|
| Journal, issue, pages | Science, Vol. 386, Issue 6724, Page eadq8587, Year 2024 |
| Publish date | Nov 22, 2024 |
Authors | Xiaoqiang Zhu / Victor Emmanuel Cruz / He Zhang / Jan P Erzberger / Joshua T Mendell / ![]() |
| PubMed Abstract | 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. ...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. |
External links | Science / PubMed:39571015 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.0 - 3.1 Å |
| Structure data | EMDB-45170, PDB-9c3h: ![]() PDB-9c3i: |
| Chemicals | ![]() ChemComp-MG: ![]() ChemComp-K: ![]() ChemComp-B3P: ![]() ChemComp-ZN: ![]() ChemComp-HOH: |
| Source |
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Keywords | RIBOSOME / mRNA degradation / CCR4-NOT complex / tRNA / TRANSCRIPTION |
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