2019
DOI: 10.1101/854810
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The Ccr4-Not complex monitors the translating ribosome for codon optimality

Abstract: Control of mRNA decay rate is intimately connected to translation elongation but the spatial coordination of these events is poorly understood. The Ccr4-Not complex initiates mRNA decay through deadenylation and activation of decapping. Using a combination of cryo-electron microscopy, ribosome profiling and mRNA stability assays we show recruitment of Ccr4-Not to the ribosome via specific interaction of the Not5 subunit with the ribosomal E-site. This interaction only occurs when the ribosome lacks acc… Show more

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Cited by 21 publications
(43 citation statements)
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“…In other organisms NOT4 contributes to post-transcriptional control as a component of the CCR4-NOT complex, central to mRNA 3′ deadenylation, promotion of decapping and subsequent mRNA decay 25,26 . NOT4 in yeast was recently shown to be essential for the turnover of mRNAs with low codon optimality during translation, triggering recruitment of the CCR4-NOT complex through catalysing ribosome ubiquitination 61 . Although the presence of NOT4 within the CCR4-NOT complex in plants has yet to be established 62 , a recent proteomic characterisation of Target of rapamycin (TOR) signalling in Arabidopsis identified NOT4A as a TOR-regulated phosphoprotein, and NOT4B as an LST8 interactor along with other conserved CCR4-NOT core subunits, suggesting the plant NOT4s may indeed be subunits within this complex 63 .…”
Section: Discussionmentioning
confidence: 99%
“…In other organisms NOT4 contributes to post-transcriptional control as a component of the CCR4-NOT complex, central to mRNA 3′ deadenylation, promotion of decapping and subsequent mRNA decay 25,26 . NOT4 in yeast was recently shown to be essential for the turnover of mRNAs with low codon optimality during translation, triggering recruitment of the CCR4-NOT complex through catalysing ribosome ubiquitination 61 . Although the presence of NOT4 within the CCR4-NOT complex in plants has yet to be established 62 , a recent proteomic characterisation of Target of rapamycin (TOR) signalling in Arabidopsis identified NOT4A as a TOR-regulated phosphoprotein, and NOT4B as an LST8 interactor along with other conserved CCR4-NOT core subunits, suggesting the plant NOT4s may indeed be subunits within this complex 63 .…”
Section: Discussionmentioning
confidence: 99%
“…The atomic models PDB 5NDG (Prokhorova et al 2017), 6FYY, 6FYX (Llacer et al , 2018), and 6TB3 (Buschauer et al 2020) containing the models for S . c .…”
Section: Methodsmentioning
confidence: 99%
“…First, the Not5 subunit interacts with Rpb4 and is required for its cytoplasmic translationrelated functions (Villanyi et al, 2014). Second, CCR4-Not promotes the degradation of inefficiently translated mRNAs by monitoring decoding rates (Webster et al, 2018;Buschauer et al, 2020). Third, together with the eIF4A2 protein, it may participate in the miRNAmediated inhibition of translation initiation of certain transcripts possessing purine-rich sequences within their 5 0 UTR (Wilczynska et al, 2019).…”
Section: Protein Factors Regulating Both Transcription and Translationmentioning
confidence: 99%