Two modes of Cue2-mediated mRNA cleavage with distinct substrate recognition initiate no-go decay

Tomomatsu, Shota; Watanabe, Atsuya; Tesina, Petr; Hashimoto, Satoshi; Ikeuchi, Ken; Li, Sihan; Matsuo, Yoshitaka; Beckmann, Roland und Inada, Toshifumi (2022): Two modes of Cue2-mediated mRNA cleavage with distinct substrate recognition initiate no-go decay. In: Nucleic Acids Research, Vol. 51, No. 1: pp. 253-270

Abstract

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 (NGD(RQC+)) or RQC uncoupled (NGD(RQC-)). 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 NGD(RQC-) but not for NGD(RQC+), and that it involves the first two N-terminal Cue domains. In contrast, Trp122 of Cue2 is crucial for NGD(RQC+). 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 (NGD(RQC-)), polyubiquitination of eS7 is recognized by two N-terminal Cue domains of Cue2. In contrast, for the cleavage within collided ribosomes (NGD(RQC+)), the UBA domain, Trp122 and the interaction between Mbf1 and uS3 are critical.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Biochemistry
• Subjects: 500 Science > 540 Chemistry
• ISSN: 0305-1048
• Language: English