Quality control and signaling pathways at stalled ribosomes

Area of Science:

• Molecular Biology
• Cellular Stress Response
• RNA Biology

Background:

• Aberrant messenger RNAs (mRNAs) result from processing errors or cellular damage.
• Translating faulty mRNAs can cause ribosome stalling, leading to incomplete and toxic polypeptides.
• Ribosome stalling is recognized by the ribosome-associated quality control (RAQC) pathway.

Purpose of the Study:

• To review the molecular mechanisms underlying ribosome stalling.
• To summarize the associated quality control and signaling pathways.
• To discuss the implications of ribosome stalling in disease and therapeutic strategies.

Main Methods:

• This review synthesizes current research on ribosome stalling.
• It examines the molecular machinery involved in recognizing and responding to stalled ribosomes.
• The review integrates findings on signaling cascades activated by ribosome collisions.

Main Results:

• Ribosome stalling triggers the RAQC pathway to degrade aberrant polypeptides.
• Ribosome collisions, a consequence of stalling, activate stress-adaptive and cell fate signaling.
• Dysregulation of these pathways is implicated in various diseases.

Conclusions:

• Understanding ribosome stalling mechanisms is crucial for cellular homeostasis.
• Targeting RAQC and related signaling pathways offers potential therapeutic avenues.
• Further research is needed to fully elucidate the role of ribosome stalling in health and disease.