Zinc finger CCHC domain-containing protein 8 (ZCCHC8)

Zinc finger CCHC domain-containing protein 8 (ZCCHC8) is a scaffolding subunit of the trimeric nuclear exosome targeting (NEXT) complex, partnering with the RNA helicase hMTR4 and the RNA-binding factor RBM7[1][2][4][5]. The NEXT complex is essential for the surveillance and exosomal degradation of various nuclear RNA species, including aberrant non-coding RNAs, promoter-upstream transcripts, enhancer RNAs, and 3'-extended products of histone and small nuclear RNA transcription[1][2][4][6][7]. ZCCHC8 has an N-terminal zinc-knuckle (CCHC-type) domain and a C-terminal proline-rich domain, facilitating its scaffolding and RNA recognition functions[1][2]. It is also required for the 3'-end maturation and exosomal targeting of the telomerase RNA component (TERC), influencing telomerase function[1][8]. Knockout of ZCCHC8 in animal models leads to developmental defects and infertility, likely due to failure in degrading retrotransposon transcripts in early embryos[2]. Mutations in ZCCHC8 are associated with rare syndromes involving pulmonary fibrosis, bone marrow failure, and telomere maintenance[1][5]. There are currently no known drugs or mechanisms of action specifically targeting ZCCHC8, nor characterized biomarkers or specific safety concerns related to therapeutic targeting.

Other names

DKFZp434E2220TRAMP-like complex RNA-binding factor ZCCHC8PFBMFT5zinc finger CCHC-type containing 8