1. Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 2QH, UK

Correspondence to: Aaron Klug¹ Email: akl@mrc-lmb.cam.ac.uk
Coordinates are deposited in the Protein Data Bank under accession code 1UN6.

Abstract

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 genome^{1, 2}. The zinc-finger motif was discovered³ during biochemical studies on the transcription factor TFIIIA, which regulates the 5S ribosomal RNA genes of Xenopus laevis^{4, 5}. Zinc-fingers mostly interact with DNA, but TFIIIA binds not only specifically to the promoter DNA, but also to 5S RNA itself^{6, 7, 8, 9}. Increasing evidence indicates that zinc-fingers are more widely used to recognize RNA^{10, 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.