# Quality control and signaling pathways at stalled ribosomes

## TL;DR

This review explains how stalled ribosomes lead to faulty proteins and how cells manage these errors to prevent disease.

## Contribution

A comprehensive review of ribosome stalling mechanisms and their role in disease and cell signaling.

## Key findings

- Ribosome stalling leads to protein misfolding and activates quality control pathways.
- Defects in ribosome-associated quality control are linked to aging and neurodegenerative diseases.
- Understanding these mechanisms could lead to new treatments for protein misfolding diseases.

## Abstract

Aberrant mRNAs can arise from errors in RNA processing or from various physicochemical insults. Ribosomes translating such faulty mRNAs may stall, producing incomplete and potentially toxic polypeptides. These aberrant translation products are eliminated by the ribosome-associated quality control pathway. Ribosome stalling also leads to ribosome collisions, which can activate signaling pathways that enable cells to adapt to stress or determine cell fate. Here, in this Review, we summarize the molecular mechanisms of ribosome stalling and the associated quality control and signaling pathways, and discuss their implications in disease and therapeutics.

Proteins sometimes fold incorrectly, which can cause problems in cells. This Review explores how ribosomes can stall and lead to protein misfolding. The researchers review how ribosome stalling happens and how cells respond, focusing on a process called ribosome-associated quality control (RQC). RQC helps degrade faulty proteins and is crucial for maintaining cell health. The study explains that ribosome stalling can occur due to damaged RNA or specific sequences in the genetic code. Cells have mechanisms to resolve these stalls, such as splitting the ribosome into parts and degrading the faulty protein. Research highlights that defects in these processes are linked to aging and diseases such as neurodegeneration. The researchers conclude that understanding RQC better could lead to new treatments for diseases caused by protein misfolding. Future research may uncover more about how cells manage protein production and maintain health.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.