PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases

Abstract The CCCH-type zinc finger (ZnF) containing ZC3H12 ribonucleases are crucial in post-transcriptional immune homoeostasis with ZC3H12A being the only structurally studied member of family. In this study, we present a structural-biochemical characterization ZC3H12C, which is linked chronic disorders like psoriasis. We established that RNA substrate cooperatively recognized by PIN and ZnF domains ZC3H12C analyzed crystal structure bound to single-stranded substrate. engages hydrogen-bonded contacts stacking interactions simultaneously. shows unprecedented structural features not previously observed any CCCH-ZnF family utilizes via unique combination spatially conserved aromatic residues align target transcript bent conformation onto scaffold. Further comparative analysis suggests trinucleotide sequence RNA. Our work describes initial structure-biochemical study on but also provides first molecular insight into recognition member. Finally, our points an evolutionary code for adopted proteins.