Zinc fingers are canonically considered DNA-binding domains, but have been more recently recognised as potential RNA binders. YY1 is a multi-functional transcription factor involved in many regulatory processes (1), binding DNA via four GLI-Krüppel-type zinc fingers. Recent evidence suggests that YY1 also interacts with RNA, acting to tether Xist non-coding RNA to the inactive X chromosome (2) or assemble Xenopus oocyte mRNP complexes (3). However, the molecular nature of the interaction is unknown.

We have shown that YY1 zinc fingers are able to bind to maximally diverse RNA sequences in EMSAs. To identify binding motifs of YY1, Systematic Evolution of Ligands by EXponential enrichment (SELEX) was used to select preferred sequences from a randomised RNA library over successive rounds of binding to a four-zinc-finger construct. The enriched libraries from each round of selection were deep sequenced, and potential binding motifs identified. One such motif was tested for binding to YY1. YY1 residues involved in the RNA interaction were identified by NMR spectroscopy and found to be distinct from the set of residues involved in DNA binding.

The work presented provides molecular detail of YY1-RNA interaction, elucidating a potentially novel mode of RNA recognition by classical zinc fingers.