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

ABSTRACT: 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.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Nicholas Luscombe

PROVIDER: PXD034483 | JPOST Repository | Thu Mar 02 00:00:00 GMT 2023

REPOSITORIES: jPOST

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			Action	DRS
	Normal_IgG_SPACE_R1.raw	Raw
	Normal_IgG_SPACE_R2.raw	Raw
	global_SPACE_C1-R1.raw	Raw
	global_SPACE_C1-R2.raw	Raw
	global_SPACE_C1-R3.raw	Raw

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Publications

RNA polymerase II-associated proteins reveal pathways affected in VCP-related amyotrophic lateral sclerosis.

Rafiee Mahmoud-Reza MR Rohban Sara S Davey Karen K Ule Jernej J Luscombe Nicholas M NM

Brain : a journal of neurology 20230601 6

Valosin-containing protein (VCP) is a hexameric ATPase associated with diverse cellular activities. Genetic mutations in VCP are associated with several forms of muscular and neuronal degeneration, including amyotrophic lateral sclerosis (ALS). Moreover, VCP mediates UV-induced proteolysis of RNA polymerase II (RNAPII), but little is known about the effects of VCP mutations on the transcriptional machinery. Here, we used silica particle-assisted chromatin enrichment and mass spectrometry to stud ...[more]

PMID: 36789492

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