Two modes of Cue2-mediated mRNA cleavage with distinct substrate recognition initiate no-go decay
Ribosome collisions are recognized by E3 ubiquitin ligase Hel2/ZNF598, leading to RQC (ribosome-associated quality control) and to endonucleolytic cleavage and degradation of the mRNA termed NGD (no-go decay). NGD in yeast requires the Cue2 endonuclease and occurs in two modes, either coupled to RQC (NGDRQC+) or RQC uncoupled (NGDRQC-). This is mediated by an unknown mechanism of substrate recognition by Cue2. Here, we show that the ubiquitin binding activity of Cue2 is required for NGDRQC- but not for NGDRQC+, and that it involves the first two N-terminal Cue domains. In contrast, Trp122 of Cue2 is crucial for NGDRQC+. Moreover, Mbf1 is required for quality controls by preventing +1 ribosome frameshifting induced by a rare codon staller. We propose that in Cue2-dependent cleavage upstream of the collided ribosomes (NGDRQC-), polyubiquitination of eS7 is recognized by two N-terminal Cue domains of Cue2. In contrast, for the cleavage within collided ribosomes (NGDRQC+), the UBA domain, Trp122 and the interaction between Mbf1 and uS3 are critical.
Authors: Tomomatsu S, Watanabe A, Tesina P, Hashimoto S, Ikeuchi K, Li S, Matsuo Y, Beckmann R, Inada T
投稿者プロフィール
最新の投稿
- 令和5年度 (FY2023)2024.03.26Induced pluripotent stem cells-based disease modeling, drug screening, clinical trials, and reverse translational research for amyotrophic lateral sclerosis
- 令和5年度 (FY2023)2024.03.26Protein profiling of extracellular vesicles from iPSC-derived astrocytes of patients with ALS/PDC in Kii peninsula
- 令和5年度 (FY2023)2024.03.26Single transcription factor efficiently leads human induced pluripotent stem cells to functional microglia
- 令和5年度 (FY2023)2023.12.08Is euchromatin really open in the cell?