Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes.

In yeast, multiprotein bridging factor 1 (Mbf1) has been proposed to function in the integrated stress response (ISR) as a transcriptional coactivator by mediating a direct interaction between general transcription machinery and the process's key effector, Gcn4. However, mounting evidence has demonstrated that Mbf1 (and its human homolog EDF1) is recruited to collided ribosomes, a known activator of the ISR. In this study, we connect these otherwise seemingly disparate functions of Mbf1.

Inability to rescue stalled ribosomes results in overactivation of the integrated stress response.

Endogenous and exogenous chemical agents are known to compromise the integrity of RNA and cause ribosome stalling and collisions. Recent studies have shown that collided ribosomes serve as sensors for multiple processes, including ribosome quality control (RQC) and the integrated stress response (ISR). Since RQC and the ISR have distinct downstream consequences, it is of great importance that organisms activate the appropriate process.