Crystal structure of a zinc-finger–RNA complex reveals two modes of molecular recognition

Zinc-finger proteins of the classical Cys2His2 type are the most frequently used class of transcription factor and account for about 3% of genes in the human genome1,2. The zinc-finger motif was discovered3 during biochemical studies on the transcription factor TFIIIA, which regulates the 5S ribosomal RNA genes of Xenopus laevis4,5. Zinc-fingers mostly interact with DNA, but TFIIIA binds not only specifically to the promoter DNA, but also to 5S RNA itself6,7,8,9. Increasing evidence indicates that zinc-fingers are more widely used to recognize RNA10,11,12,13. There have been numerous structural studies on DNA binding14, but none on RNA binding by zinc-finger proteins. Here we report the crystal structure of a three-finger complex with 61 bases of RNA, derived15 from the central regions of the complete nine-finger TFIIIA–5S RNA complex. The structure reveals two modes of zinc-finger binding, both of which differ from that in common use for DNA: first, the zinc-fingers interact with the backbone of a double helix; and second, the zinc-fingers specifically recognize individual bases positioned for access in otherwise intricately folded ‘loop’ regions of the RNA.