Seminars of Interest

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Photo of Prof. Zaher. He's wearing a blue, longsleeve shirt.

Biochemistry Seminar of Special Interest: Dr. Hani Zaher (Washington University in St. Louis), "Ribosome collisions, quality control and stress response"

Event Type
Dr. Hong Jin
Mar 4, 2022   12:00 pm  
Assoc. Prof. Hani Zaher
Cara Day
Originating Calendar
Biochemistry Department Seminars

During protein synthesis, the ribosome integrates multiple cues to ensure that the correct protein is made at the right place, the right time and at the right concentration. These cues are the result of signals triggered by varying cellular needs and environmental conditions such as proliferation and stress. In eukaryotes, the integrated-stress response (ISR) responds to stresses through the activation of kinases that act on the initiation factor eIF2. Phosphorylation of eIF2represses global translation, but also derepresses translation of key pro-survival mRNAs. In yeast, ISR is activated by the eIF2kinase Gcn2. Recent studies from several groups, including ours, have pointed to a central role for ribosomes and in particular their stalling during the activation of ISR. Interestingly, ribosome stalling also activates ribosome-quality control (RQC), which depends critically on an E3 ligase Hel2. Previously, we established that Hel2 is activated in response to ribosome collisions and showed that chemical insults that damage RNA trigger RQC. Notably, these very same agents also activate ISR, suggesting that RQC and ISR are tightly be coordinated. In a recent study, we showed that not only do ribosome collisions activate both processes, but that the activation of one suppresses that of the other. Emerging from these studies is the observation that collided ribosomes are widely used as sensors to trigger an appropriate response, depending on the type and level of stress.

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