ALS-associated FUS mutation reshapes the RNA and protein composition of stress granules.

Autor:	Mariani D; Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16153, Genoa, Italy.; Department of Biology and Biotechnologies 'C. Darwin', Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy., Setti A; Department of Biology and Biotechnologies 'C. Darwin', Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy., Castagnetti F; Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16153, Genoa, Italy., Vitiello E; Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16153, Genoa, Italy., Stufera Mecarelli L; Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16153, Genoa, Italy.; Department of Biology and Biotechnologies 'C. Darwin', Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy., Di Timoteo G; Department of Biology and Biotechnologies 'C. Darwin', Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy., Giuliani A; Department of Biology and Biotechnologies 'C. Darwin', Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy., D'Angelo A; Department of Biology and Biotechnologies 'C. Darwin', Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy., Santini T; Department of Biology and Biotechnologies 'C. Darwin', Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy., Perego E; Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16153, Genoa, Italy., Zappone S; Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16153, Genoa, Italy., Liessi N; Analytical Chemistry Lab, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genoa, Italy., Armirotti A; Analytical Chemistry Lab, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genoa, Italy., Vicidomini G; Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16153, Genoa, Italy., Bozzoni I; Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16153, Genoa, Italy.; Department of Biology and Biotechnologies 'C. Darwin', Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.; Center for Life Nano-& Neuro-Science, Fondazione Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161, Rome, Italy.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Nov 27; Vol. 52 (21), pp. 13269-13289.
DOI:	10.1093/nar/gkae942
Abstrakt:	Stress granules (SG) are part of a cellular protection mechanism where untranslated messenger RNAs and RNA-binding proteins are stored upon conditions of cellular stress. Compositional variations due to qualitative or quantitative protein changes can disrupt their functionality and alter their structure. This is the case of different forms of amyotrophic lateral sclerosis (ALS) where a causative link has been proposed between the cytoplasmic de-localization of mutant proteins, such as FUS (Fused in Sarcoma), and the formation of cytotoxic inclusions. Here, we describe the SG transcriptome in neuroblastoma cells and define several features for RNA recruitment in these condensates. We demonstrate that SG dynamics and RNA content are strongly modified by the incorporation of mutant FUS, switching to a more unstructured, AU-rich SG transcriptome. Moreover, we show that mutant FUS, together with its protein interactors and their target RNAs, are responsible for the reshaping of the mutant SG transcriptome with alterations that can be linked to neurodegeneration. Our data describe the molecular differences between physiological and pathological SG in ALS-FUS conditions, showing how FUS mutations impact the RNA and protein composition of these condensates. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu