Exosome complex component CSL4 (EXOSC1)

Exosome complex component CSL4 (EXOSC1) is a non-catalytic, peripheral subunit of the multi-protein RNA exosome complex, which is essential for 3'→5' RNA degradation and processing in both the nucleus and the cytoplasm. The exosome complex is responsible for maturation of stable RNA species (rRNA, snRNA, snoRNA), elimination of aberrant or non-coding RNAs, general turnover of mRNA (including those with AU-rich elements), and RNA surveillance pathways, thus preventing accumulation of defective RNAs. As part of the S1/KH cap of the exosome core, EXOSC1 is essential for binding nascent RNA and stabilizing the exosome structure. New evidence suggests that in certain contexts, such as kidney cancer, EXOSC1 can act independently of the full exosome complex, cleaving single-stranded DNA and promoting DNA damage, thus creating a unique role in DNA mutagenesis and therapeutic sensitization to PARP inhibitors. Loss of EXOSC1 is developmentally lethal in mice, underlining its critical function in cellular RNA metabolism. There are currently no approved therapeutics directly targeting EXOSC1, but its potential as a biomarker or sensitizer to DNA repair-targeted therapies is under investigation.

Other names

Exosome component 1CSL4CGI-108hCsl4pCsl4pSki4pSKI4p13exosome complex component CSL43'-5' exoribonuclease CSL4 homologexosomal core protein CSL4homolog of yeast exosomal core protein CSL4PCH1F

Not a classical drug target; however, loss or inhibition of EXOSC1 may increase DNA damage and sensitize cells to DNA repair inhibitors such as PARP inhibitors