Failure of RQC machinery causes protein aggregation and proteotoxic stress
Translation of messenger RNAs lacking a stop codon results in the addition of a carboxy-terminal poly-lysine tract to the nascent polypeptide, causing ribosome stalling. Non-stop proteins and other stalled nascent chains are recognized by the ribosome quality control (RQC) machinery and targeted for proteasomal degradation. Failure of this process leads to neurodegeneration by unknown mechanisms. Here we show that deletion of the E3 ubiquitin ligase Ltn1p in yeast, a key RQC component, causes stalled proteins to form detergent-resistant aggregates and inclusions. Aggregation is dependent on a C-terminal alanine/threonine tail that is added to stalled polypeptides by the RQC component, Rqc2p. Formation of inclusions additionally requires the poly-lysine tract present in non-stop proteins. The aggregates sequester multiple cytosolic chaperones and thereby interfere with general protein quality control pathways. These findings can explain the proteotoxicity of ribosome-stalled polypeptides and demonstrate the essential role of the RQC in maintaining proteostasis.
Nature doi: 10.1038/nature16973
STRATEGIES FOR A COMPANY’S INTELLECTUAL PROPERTY. IP protection is a part of your business strategy and matches your commercial goals. A simple IP strategy is to protect your product and service by getting patent, trademark and copyright certificates.
U.S. COMPANY REGISTRATION. We help our foreign clients with registering U.S. business to support moving their innovations to U.S. market. We assist in navigating the process of setting up a new business and support while it grows.