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

Nature volume 426, pages 96–100 (2003)Cite this article

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 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.

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Figure 1: Components of the zinc-finger–RNA complex.
Figure 2: Interactions of the three-finger peptide with the RNA.
Figure 3: Recognition of loop E by finger 4.
Figure 4: Recognition of loop A by finger 6.

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Acknowledgements

We acknowledge the Daresbury Laboratory and the ESRF for provision of facilities. We thank P. Evans and other colleagues for advice and help. D.L. was initially supported by a grant from the Human Frontier Science Programme (to A.K.) and later by a Fellowship from the Sino-British Fellowship Trust.

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

    Duo Lu, M. Alexandra Searles & Aaron Klug

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  1. Duo Lu
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Correspondence to Aaron Klug.

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Lu, D., Alexandra Searles, M. & Klug, A. Crystal structure of a zinc-finger–RNA complex reveals two modes of molecular recognition. Nature 426, 96–100 (2003). https://doi.org/10.1038/nature02088

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