Proteins co-localized with RNA Pol2 in ALS patient-derived neural precursors

Deficiency of proteostasis and RNA metabolism are increasingly recognized as critical drivers of neurodegenerative diseases. In this study, we focused on RNA polymerase II (Pol2) as the converging point of these two elements to understand how transcriptional machinery is affected by ALS-associated VCP mutations. Pol2 highly depends on its accessory factors to initiate, elongate, and terminate the transcription properly with accurate RNA splicing and processing. We, therefore, studied proteins co-localised with Pol2 in neural precursors obtained from ALS-patient iPS cells. To do that, we used the SPACE method as a highly sensitive proteomic tool to eliminate the artificial interactions during purification.