FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons

Abstract The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Here we report that FUS controls back-splicing reactions leading to circular RNA (circRNA) production. We identified circRNAs expressed in in vitro -derived mouse motor neurons (MNs) and determined that the production of a considerable number of these circRNAs is regulated by FUS. Using RNAi and overexpression of wild-type and ALS-associated FUS mutants, we directly correlate the modulation of circRNA biogenesis with alteration of FUS nuclear levels and with putative toxic gain of function activities. We also…

• JA
  Judith and Jean Pape Adams Charitable Foundation
• FR
  Fondazione Roma
• NI
  National Institutes of Health
• NI
  National Institute of Neurological Disorders and Stroke