News Releases & Research Results Reproduction of the forced termination of aberrant translational retardation in vitro - Mechanism of the fate determination of a nascent peptide chain by ribosome ubiquitination -

The results of research conducted by Professor Toshifumi Inada and Assistant Professor Yoshitaka Matsuo of the Graduate School of Pharmaceutical Sciences, Tohoku University, Professor Roland Beckmann of the University of Munich (Germany), and Depositing Principal Investigator Yasushi Saeki of the Tokyo Metropolitan Institute of Medical Science.

• An endogenous sequence leading to protein degradation due to potent translational retardation during gene expression was identified for the first time in the world.
• The following four-step reaction in the molecular mechanism of RQC (Ribosome Quality Control) to recognize aberrant translation was successfully reproduced for the first time in the world using the endogenous sequence: (1) translational retardation, (2) ribosomal collision (*1), (3) ubiquitination of the collided ribosomes (*2), and (4) subunit dissociation of the ubiquitinated ribosomes.
  *1: A protein synthetic apparatus that combines amino acids according to the genetic information of mRNA, i.e., a huge complex composed of proteins and RNAs.
  *2: Covalent addition of ubiquitin, a low-molecular-weight protein consisting of 76 amino acids, to the lysine residues of other proteins controls protein activation and facilitates degradation by proteasomes, which recognize and degrade abnormal ubiquitinated proteins.
• Breakdown of protein homeostasis due to aberrant translation causes neurodegenerative diseases such as autism.
• The results of the research should provide a solid foundation for understanding their developmental mechanisms.

This research was conducted with the support of the Advanced Research & Development Programs for Medical Innovation (AMED-CREST) by AMED.

The results of research were published online in the American scientific journal, Nature Structural & Molecular Biology, on March 24.

Matsuo Y., et al. RQT complex dissociates ribosomes collided on endogenous RQC substrate SDD1 Structural & Molecular Biology
DOI：10.7554/eLife.45145.001