Many different RNA species play an important role in the regulation of gene expression in higher organisms, and RNA-binding proteins (RBPs) help mediate the function of both coding and non-coding RNAs. Zinc fingers are classically considered DNA-binding domains, but many have now been recognised as potential RNA binders. YY1 is a multi-functional transcription factor involved in many regulatory processes (reviewed in (1)). It binds DNA via four GLI-Krüppel type zinc fingers, and evidence suggests that these domains also interact with physiological RNA (2) (3); however, the sequence specificity of the interaction is unknown.

Using a four-zinc-finger construct of YY1, Systematic Evolution of Ligands by EXponential enrichment (SELEX) was used to enrich preferred sequences from a randomised RNA library over successive rounds of  binding to the protein, and the enriched libraries from each round of selection were deep sequenced (Bind-n-Seq (4)). A bioinformatics pipeline adapted from the Korf lab (UC Davis) was used to analyse the Bind-n-Seq data, identifying at least one strongly enriched motif. This is an intriguing result as the YY1 RNA recognition site has not previously been defined at the nucleotide level. Once validated, these sequences will serve as a basis for functional characterisation of YY1 as an RNA-binding protein.