9c3i
From Proteopedia
Rebuilt CNOT3/tRNA-LEU structure
Structural highlights
DiseaseCNOT3_HUMAN Precursor T-cell acute lymphoblastic leukemia. FunctionCNOT3_HUMAN Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. May be involved in metabolic regulation; may be involved in recruitment of the CCR4-NOT complex to deadenylation target mRNAs involved in energy metabolism. Involved in mitotic progression and regulation of the spindle assembly checkpoint by regulating the stability of MAD1L1 mRNA. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may involve histone deacetylases. Involved in the maintenance of emryonic stem (ES) cell identity.[1] [2] [3] Publication Abstract from PubMedThe 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. Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes.,Zhu X, Cruz VE, Zhang H, Erzberger JP, Mendell JT Science. 2024 Nov 22;386(6724):eadq8587. doi: 10.1126/science.adq8587. Epub 2024 , Nov 22. PMID:39571015[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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