Valosin-containing protein (VCP) mRNA 3′ untranslated region (VCP mRNA 3′UTR)

Valosin-containing protein (VCP), also known as p97, is a member of the AAA+ ATPase family that functions as a molecular chaperone to segregate ubiquitinated proteins from complexes for degradation [UniProt: P55072]. The 3′ untranslated region (3′UTR) of the VCP mRNA serves as a regulatory hub, containing binding sites for microRNAs and RNA-binding proteins that control the transcript's stability and translation efficiency [PubMed: 28818859]. Mutations in VCP or its dysregulation are central to the pathogenesis of multisystem proteinopathy, including inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD), as well as amyotrophic lateral sclerosis (ALS) [NIH: GARD]. Therapeutic targeting of the VCP mRNA 3′UTR, primarily through antisense oligonucleotides (ASOs) or microRNA mimics like miR-129-5p, aims to reduce VCP protein levels in contexts of overexpression or toxic gain-of-function [PubMed: 28818859]. This approach is particularly relevant in oncology, where VCP is often upregulated to support the high metabolic and proteostatic demands of cancer cells [PubMed: 23603127]. However, because VCP is essential for cellular homeostasis, therapeutic strategies must achieve precise knockdown to avoid systemic toxicity or lethality.

Other names

p97 mRNA 3′UTRTERA mRNA 3′UTRCDC48 mRNA 3′UTRValosin-containing protein mRNA 3′UTR

Binding of antisense oligonucleotides or microRNA mimics to the 3′UTR to promote RNase H-mediated mRNA degradation or inhibit translation of the VCP protein.