9C3I

Rebuilt CNOT3/tRNA-LEU structure

Summary for 9C3I

• Entry DOI: 10.2210/pdb9c3i/pdb
• Related: 9C3H
• EMDB information: 16052 45170
• Descriptor: CCR4-NOT transcription complex subunit 3, tRNA Leu, UAA-1-1 (2 entities in total)
• Functional Keywords: mrna degradation, ccr4-not complex, trna, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 91856.31

Authors

Erzberger, J.P.,Cruz, V.E. (deposition date: 2024-06-01, release date: 2024-12-04)

Primary citation

Zhu, X.,Cruz, V.E.,Zhang, H.,Erzberger, J.P.,Mendell, J.T.
Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes.
Science, 386:eadq8587-eadq8587, 2024

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. 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.

PubMed: 39571015
DOI: 10.1126/science.adq8587

Experimental method

ELECTRON MICROSCOPY (3.1 Å)