Wild-type FUS corrects ALS-like disease induced by cytoplasmic mutant FUS through autoregulation.

ABSTRACT: Mutations in FUS, an RNA-binding protein involved in multiple steps of RNA metabolism, are associated with the most severe forms of amyotrophic lateral sclerosis (ALS). Accumulation of cytoplasmic FUS is likely to be a major culprit in the toxicity of FUS mutations. Thus, preventing cytoplasmic mislocalization of the FUS protein may represent a valuable therapeutic strategy. FUS binds to its own pre-mRNA creating an autoregulatory loop efficiently buffering FUS excess through multiple proposed mechanisms including retention of introns 6 and/or 7. Here, we introduced a wild-type FUS gene allele, retaining all intronic sequences, in mice whose heterozygous or homozygous expression of a cytoplasmically retained FUS protein (Fus^∆NLS) was previously shown to provoke ALS-like disease

SUBMITTER: Sanjuan-Ruiz I 

PROVIDER: S-EPMC8419956 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature