FUS-SMN Protein Interactions Link the Motor Neuron Diseases ALS and SMA

• DOI: 10.1016/j.celrep.2012.08.025
• Publication Date: 2012-09-27T11:23:47Z
• Authors: Tomohiro Yamazaki; Shi Chen; Yong Yu; Biao Yan; Tyler C. Haertlein; Monica A. Carrasco; Juan C. Tapia; Bo Zhai; Rita Das; Melanie Lalancett...; Aarti Sharma; Siddharthan Chandran; Gareth Sullivan; Agnes Lumi Nishimura; Christopher E. Shaw; Steve P. Gygi; Neil A. Shneider; Tom Maniatis; Robin Reed
• Keywords: snRNP

Mutations in the RNA binding protein FUS cause amyotrophic lateral sclerosis (ALS), a fatal adult motor neuron disease. Decreased expression of SMN causes childhood disorder spinal muscular atrophy (SMA). The complex localizes both cytoplasm and nuclear Gems, loss Gems is cellular hallmark fibroblasts patients with SMA. Here, we report that associates complex, mediated by U1 snRNP direct interactions between SMN. Functionally, show required for Gem formation HeLa cells, containing severe ALS-causing mutation (R495X) also results loss. Strikingly, reduction observed ALS patient expressing either mutant or TDP-43, another interacts FUS. physical functional among SMN, FUS, indicate SMA share biochemical pathway, providing strong support view these diseases are related.