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Learn MoreThe majority of individuals with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) exhibit neuronal cytoplasmic inclusions rich in the RNA binding protein TDP43. Even so, the relationship between TDP43s RNA binding properties and neurodegeneration remain obscure. Here we show that engineered mutations disrupting a salt bridge between TDP43s RNA recognition motifs interfere with nucleic acid binding and eliminate recognition of native TDP43 substrates. The accumulation of WT TDP43, but not RNA binding-deficient variants, disproportionately affected the abundance and splicing of encoding ribosome and oxidative phosphorylation components. SOURCE: Sami Barmada (sbarmada@med.umich.edu) - University of Michigan
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