Speaker: Prof. Dr. Claudio Joazeiro - Center for Molecular Biology (ZMBH) - Affiliate, Interdisciplinary Center for Neurosciences (IZN) - Universität Heidelberg, Germany.
Presentation
Speaker: Prof. Dr. Claudio Joazeiro - Center for Molecular Biology (ZMBH) - Affiliate, Interdisciplinary Center for Neurosciences (IZN) - Universität Heidelberg, Germany.
Host: Dr. Cristina Mayor-Ruiz, Junior Group Leader - Targeted protein degradation and drug discovery Lab. - IRB Barcelona - Mechanisms of Disease Programme.
Date: Friday 27 January 2023, 12.00h
Place: Fèlix Serratosa
IMPORTANT: For attendees outside the PCB community you must register at least 24h before the seminar.
Abstract
Ribosomes can stall before protein synthesis is completed for various reasons, such as amino acid starvation. Among critical problems caused by ribosome stalling is the production of truncated nascent chains that are potentially toxic. We originally discovered Ribosome-associated Quality Control (RQC) as a protein quality control pathway that targets those aberrant nascent chains for degradation, and whose defect causes ALS-like neurodegeneration in mice. More recently, we have found that bacteria also have an ancestral RQC pathway. In my talk I will present our findings on the mechanisms and evolution of RQC, along with the status of the field, including the recent realization that ribosome stalling leads to a more complex cellular response than previously appreciated—ribosome stalling causes collisions with trailing ribosomes; in addition to promoting decay of the associated nascent chain and mRNA, collided 'disomes' elicit innate immunity as well as stress signaling by GCN2, p38 and JNK kinases, to confer cellular protection and regulate cell fate decisions. Finally, I will present new directions our laboratory is taking, particularly towards the study of ribosome stalling and RQC in the context of normal physiology, aging, and disease.