Fused in Sarcoma (FUS) Targets Neuronal G Quadruplex Containing mRNAS.

Abstract

Fused in sarcoma (FUS), identified as the heterogeneous nuclear ribonucleoprotein P2, is expressed in neuronal and non-neuronal tissue, and has the ability to shuttle between the nucleus and cytoplasm. Among other functions, FUS has been implicated in mRNA transport and the deletion of FUS in cultured hippocampal cells has been shown to result in abnormal spine and dendrite morphology. This evidence suggests that FUS may have a role in synaptic function regulation, potentially through a mechanism involving the transport and translation of neuronal mRNAs. We hypothesize that FUS is able to target neuronal mRNAs forming G quadruplex structures in their 3′-untranslated region (UTR). This study used electrophoretic mobility shift assays and steady-state fluorescence spectroscopy to analyze the binding of the C-terminal RGG box and of the full-length FUS to RNA G quadruplex structures formed in the 3′-UTR of the post-synaptic density (PSD) 95 and Shank1 mRNAs.