Exosome component 9 (EXOSC9)

Exosome component 9 (EXOSC9) is a non-catalytic core subunit of the highly conserved RNA exosome complex, a multi-protein ribonuclease machine responsible for the 3′-5′ degradation and processing of a wide variety of RNA substrates in both the nucleus and cytoplasm[1][3][4]. EXOSC9 is integral for the processing of stable RNA species (such as rRNA, snRNA, snoRNA), degradation of defective or superfluous mRNAs, surveillance of non-coding and pervasive transcripts, and is implicated in the decay of specific lncRNAs involved in telomeric integrity maintenance[1][2][3][4]. Independently of the full exosome complex, EXOSC9 is recruited to telomeres by SUMOylated HP1α, where it specifically regulates the degradation of TERRA, a telomeric lncRNA, thus modulating chromatin states and influencing genome stability in hormone receptor-positive breast cancer cells[2]. Variants in EXOSC9 cause rare but severe neurodevelopmental syndromes such as pontocerebellar hypoplasia with motor neuronopathy, indicating its vital role in RNA homeostasis required for neuronal development[1][3][5]. EXOSC9 also serves as an autoantigen (PM/Scl-75) in polymyositis-scleroderma overlap syndrome, linking it to autoimmune pathogenesis[1][3]. Though not a direct therapeutic target, EXOSC9 expression has been associated with cellular adaptation to stress, P-body formation, and sensitivity to specific cancer therapies[2][5].

Other names

Exosome complex component RRP45PMSCL1PM/Scl-75Rrp45pRRP45p5p6Autoantigen PM/Scl 1P75 polymyositis-scleroderma overlap syndrome-associated autoantigenPolymyositis/scleroderma autoantigen 1Polymyositis/scleroderma autoantigen 75 kDaPolymyositis/scleroderma autoantigen 1 (75kD)PCH1DPMSCL autoantigen, 75kDexosome complex exonuclease RRP45

Olaparib sensitivity: Cells with high EXOSC9 expression levels in hormone receptor-positive, endocrine therapy-resistant breast cancer show increased sensitivity to PARP inhibition, possibly due to increased telomeric DNA damage and altered TERRA degradation[2]. No small molecule or biologic directly targets EXOSC9 for therapeutic effect as of current literature.