Defective ribosomes activate ribosome-associated quality control pathway

• Main Author: Pek, Jonetta Shi Qi
• Other Authors: Choe Young Jun
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2021
• Subjects: Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/148577
• Institution: Nanyang Technological University

Maintaining cellular proteome integrity is crucial for normal cell functioning and survival as dysfunction to proteostasis gives rise to aging-related diseases. Cells have evolved a multitude of protein surveillance machineries to monitor the cytosol for aberrant proteins, including the ribosome-associated quality control (RQC) pathway which targets aberrant nascent chains at their birthplace. Characterisation of stalling-inducing aberrant transcripts has been the focus of most research in the last decade. In this FYP, however, I demonstrated that defects in ribosome itself can also trigger the RQC pathway. First, I analysed toxic effects of stall-inducing aberrant mRNAs. The observed toxicity prompted me to examine if genetic mutations for ribosomal proteins also display toxicity, reflecting increased ribosomal stalling. 19 ribosomal mutants were examined in this study to investigate relationship between ribosomal defects and the RQC pathway. I discovered that two yeast strains, deleted for ribosomal protein genes RPS1B and RPL24, display greater incidence of ribosomal stalling. Eukaryotic ribosomes consist of ~80 proteins and this study shows that mutations in those ribosomal proteins can lead to increased ribosomal stalling. Although molecular mechanisms underlying defective ribosome stalling remain to be elucidated, this study will expand our understanding of when and how the RQC pathway protects cells.