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| Item Type: | Article |
|---|---|
| Title: | Mutant FUS and ELAVL4 (HuD) aberrant crosstalk in amyotrophic lateral sclerosis |
| Creators Name: | De Santis, R., Alfano, V., de Turris, V., Colantoni, A., Santini, L., Garone, M.G., Antonacci, G., Peruzzi, G., Sudria-Lopez, E., Wyler, E., Anink, J.J., Aronica, E., Landthaler, M., Pasterkamp, R.J., Bozzoni, I. and Rosa, A. |
| Abstract: | Amyotrophic lateral sclerosis (ALS) has been genetically linked to mutations in RNA-binding proteins (RBPs), including FUS. Here, we report the RNA interactome of wild-type and mutant FUS in human motor neurons (MNs). This analysis identified a number of RNA targets. Whereas the wild-type protein preferentially binds introns, the ALS mutation causes a shift toward 3′ UTRs. Neural ELAV-like RBPs are among mutant FUS targets. As a result, ELAVL4 protein levels are increased in mutant MNs. ELAVL4 and mutant FUS interact and co-localize in cytoplasmic speckles with altered biomechanical properties. Upon oxidative stress, ELAVL4 and mutant FUS are engaged in stress granules. In the spinal cord of FUS ALS patients, ELAVL4 represents a neural-specific component of FUS-positive cytoplasmic aggregates, whereas in sporadic patients it co-localizes with phosphorylated TDP-43-positive inclusions. We propose that pathological mutations in FUS trigger an aberrant crosstalk with ELAVL4 with implications for ALS. |
| Keywords: | FUS, ELAVL4, HuD, Amytrophic Lateral Sclerosis, Motor Neuron, PAR-CLIP, TDP-43, Stress Granules, RNA-Binding Protein, Brillouin |
| Source: | Cell Reports |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 27 |
| Number: | 13 |
| Page Range: | 3818-3831 |
| Date: | 25 June 2019 |
| Official Publication: | https://doi.org/10.1016/j.celrep.2019.05.085 |
| PubMed: | View item in PubMed |
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