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Structure paper

TitleSpecific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes.
Journal, issue, pagesScience, Vol. 386, Issue 6724, Page eadq8587, Year 2024
Publish dateNov 22, 2024
AuthorsXiaoqiang Zhu / Victor Emmanuel Cruz / He Zhang / Jan P Erzberger / Joshua T Mendell /
PubMed AbstractThe 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 linksScience / PubMed:39571015 / PubMed Central
MethodsEM (single particle)
Resolution2.0 - 3.1 Å
Structure data

EMDB-45170, PDB-9c3h:
Structure of the CNOT3-bound human 80S ribosome with tRNA-ARG in the P-site.
Method: EM (single particle) / Resolution: 2.0 Å

PDB-9c3i:
Rebuilt CNOT3/tRNA-LEU structure
Method: ELECTRON MICROSCOPY / Resolution: 3.1 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-B3P:
2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL / pH buffer*YM

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • oryctolagus cuniculus (rabbit)
KeywordsRIBOSOME / mRNA degradation / CCR4-NOT complex / tRNA / TRANSCRIPTION

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