26S proteasome non-ATPase regulatory subunit 3 (PSMD3) mRNA (PSMD3 mRNA)

26S proteasome non-ATPase regulatory subunit 3 (PSMD3) mRNA is the transcript encoding a critical component of the 19S regulatory particle of the 26S proteasome [UniProt KB: O43242]. This subunit is essential for the recognition, unfolding, and translocation of ubiquitinated proteins into the 20S catalytic core for degradation, thereby maintaining cellular protein homeostasis [NCBI Gene: 5709]. PSMD3 is frequently overexpressed in various malignancies, particularly in HER2-positive breast cancer, where it is located on the 17q12-21 amplicon and serves as a key driver of cell proliferation and survival [PMID: 28652445]. Targeting the PSMD3 mRNA using RNA interference (RNAi) or antisense oligonucleotides (ASOs) has been shown in preclinical models to induce proteotoxic stress and apoptosis by depleting the PSMD3 protein and disrupting proteasome assembly [PMID: 31110218]. Beyond oncology, genetic variants in the PSMD3 locus have been associated with metabolic traits, including obesity and type 2 diabetes, suggesting a broader role in systemic metabolism [PMID: 25607358]. While no PSMD3 mRNA-targeted therapies are currently FDA-approved, the transcript remains a significant target for the development of precision RNA-based therapeutics.

Other names

RPN3P58S3Proteasome 26S subunit non-ATPase 326S proteasome regulatory subunit RPN3

Targeted degradation of PSMD3 mRNA via RNA interference (RNAi) or antisense mechanisms, resulting in the depletion of the PSMD3 protein and subsequent inhibition of 26S proteasome assembly and function.