TDP-43 knockdown in primary rat astrocytes

TDP-43 is an RNA binding protein involved in amyotrophic lateral sclerosis and other neurodegenerative diseases. The purpose of this study was to determine if loss of TDP-43 function leads to accumulation of repetitive element transcripts, double-stranded RNA (dsRNA) and innate immune activation that may be involved in disease pathology. TDP-43 was knocked down in primary rat astrocytes via siRNA, cells were treated with/without ATP (an immune modulator), and polyA RNA-seq was performed to profile gene expression. Immunoprecipitation/RNA-seq was also performed using a dsRNA-specific antibody to identify potential dsRNAs resulting from TDP-43 knockdown. PolyA RNA and/or immunoprecipitated total RNA from cells treated with TDP-43 siRNA, scrambled (control) siRNA and/or ATP