The ribosome as a platform to coordinate mRNA decay

Abstract

Messenger RNA (mRNA) homeostasis is a critical aspect of cellular function, involving the dynamic interplay between transcription and decay processes. Recent advances have revealed that the ribosome plays a central role in coordinating mRNA decay, challenging the traditional view that free mRNA is the primary substrate for degradation. This review examines the mechanisms whereby ribosomes facilitate both the licensing and execution of mRNA decay. This involves factors such as the Ccr4–Not complex, small MutS-related domain endonucleases, and various quality control pathways. We discuss how translational fidelity, as well as the presence of nonoptimal codons and ribosome collisions, can trigger decay pathways such as nonstop decay and no-go decay. Furthermore, we highlight the direct association of canonical exonucleases, such as Xrn1 and the Ski-exosome system, with the ribosome, underscoring the ribosome’s multifaceted role as a platform for regulatory processes governing mRNA stability. By integrating recent findings, this review offers a comprehensive overview of the structural basis of how ribosomes not only facilitate translation but also serve as critical hubs for mRNA decay coordination.