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Role of the ribosomal quality control machinery in nucleocytoplasmic translocation of polyQ-expanded huntingtin exon-1.

Biochem Biophys Res Commun. 2017 Aug 29. pii: S0006-291X(17)31709-6. doi: 10.1016/j.bbrc.2017.08.126. [Epub ahead of print]

Authors/Editors: Zheng J, Yang J, Choe YJ, Hao X, Cao X, Zhao Q, Zhang Y, Franssens V, Hartl FU, Nyström T, Winderickx J, Liu B.
Publication Date: 2017



The subcellular localization of polyQ-expanded huntingtin exon1 (Httex1) modulates polyQ toxicity in models of Huntington's disease. Using genome-wide screens in a yeast model system, we report that the ribosome quality control (RQC) machinery, recently implicated in neurodegeneration, is a key determinant for the nucleocytoplasmic distribution of Httex1-103Q. Deletion of the RQC genes, LTN1 or RQC1, caused the accumulation of Httex1-103Q in the nucleus through a process that required the CAT-tail tagging activity of Rqc2 and transport via the nuclear pore complex. We provide evidence that nuclear accumulation of Httex1-103Q enhances its cytotoxicity, suggesting that the RQC machinery plays an important role in protecting cells against the adverse effects of polyQ expansion proteins.

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