Engineering sequence specificity in an RNA-binding zinc finger protein

Abstract

Targeting and manipulating endogenous RNAs in a sequence-specific manner is important for both understanding RNA biology and developing RNA-targeting therapeutics. RNA-recognizing zinc fingers (ZnFs) are excellent candidates as designer proteins to expand the RNA-targeting toolbox due to their compact size (∼3 kDa each) and modular sequence recognition. Previous research showed that a single ZnF in ZRANB2 recognizes a single-strand RNA containing a GGU motif with micromolar affinity. Although structures of ZRANB2 ZnF in complex with the RNA have been solved, rules that govern its sequence-specific recognition are still unclear for engineering purpose.