SynGAP variant from Japanese ALS cohort alters the recruitment of RNA binding proteins

ABSTRACT: FUS is one of the pathogenic RNA-binding proteins for amyotrophic lateral sclerosis (ALS). We previously reported that FUS stabilized SynGAP mRNA at its 3’UTR and maintained spine maturation and cognitive function in mice. To elucidate whether this mechanism could be pathogenic for ALS, we identified SynGAP 3’UTR variant at the binding site of FUS, different from that in mice, from a multicenter cohort in Japan. Human induced pluripotent stem cells (hiPSC)-derived motor neurons with SynGAP variant showed spine abnormality with aberrant SynGAP splicing. To evaluate how SynGAP variant altered the access of RNA binding proteins to SynGAP 3'UTR, we performed pull down assay by using biotinylated RNA probes with or without the variant.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Motor Neuron, Cell Culture

DISEASE(S): Amyotrophic Lateral Sclerosis

SUBMITTER: Satoshi Yokoi  

LAB HEAD: Masahisa Katsuno

PROVIDER: PXD026586 | Pride | 2023-03-11

REPOSITORIES: pride