Dysregulated ribosome quality control in human diseases

Precise regulation of mRNA translation is of fundamental importance for maintaining homeostasis. Conversely, dysregulated general or transcript-specific translation, as well as abnormal translation events, have been linked to a multitude of diseases. However, driven by the misconception that the transient nature of mRNAs renders their abnormalities inconsequential, the importance of mechanisms that monitor the quality and fidelity of the translation process has been largely overlooked. In recent years, there has been a dramatic shift in this paradigm, evidenced by several seminal discoveries on the role of a key mechanism in monitoring the quality of mRNA translation - namely, Ribosome Quality Control (RQC) - in the maintenance of homeostasis and the prevention of diseases. Here, we will review recent advances in the field and emphasize the biological significance of the RQC mechanism, particularly its implications in human diseases.

Ensuring the synthesis of full-length, correctly folded proteins is vital for maintaining homeostasis. If a translating ribosome stalls, the trailing ribosomes collide into it, which if left unresolved leads to deleterious effects on the cell due to the accumulation of protein aggregates. Ribosome Quality Control (RQC) detects the collided ribosomes and removes the aberrant mRNA and nascent peptide. Conversely, dysfunctional RQC or excessive ribosome collisions that overwhelm RQC can lead to proteotoxicity and diseases. image