期刊
EMBO REPORTS
卷 21, 期 10, 页码 -出版社
WILEY
DOI: 10.15252/embr.201949585
关键词
motor neurone disease; neurodegeneration; phase transition; protein precipitation; ribonuclease
资金
- Barts Charity
- Queen Mary Innovation
- Medical Research Council
- Motor Neurone Disease Association
- Rosetrees Trust
- Wellcome Trust Value in People Award
Most proteins in cell and tissue lysates are soluble. We show here that in lysate from human neurons, more than 1,300 proteins are maintained in a soluble and functional state by association with endogenousRNA, as degradation ofRNAinvariably leads to protein aggregation. The majority of these proteins lack conventionalRNA-binding domains. Using synthetic oligonucleotides, we identify the importance of nucleic acid structure, with single-stranded pyrimidine-rich bulges or loops surrounded by double-stranded regions being particularly efficient in the maintenance of protein solubility. These experiments also identify an apparent one-to-one protein-nucleic acid stoichiometry. Furthermore, we show that protein aggregates isolated from brain tissue from Amyotrophic Lateral Sclerosis patients can be rendered soluble after refolding by bothRNAand synthetic oligonucleotides. Together, these findings open new avenues for understanding the mechanism behind protein aggregation and shed light on how certain proteins remain soluble.
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