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The intrinsic structure of poly(A) RNA determines the specificity of Pan2 and Caf1 deadenylases

DOI: 10.1038/s41594-019-0227-9 DOI Help

Authors: Terence T. L. Tang (MRC Laboratory of Molecular Biology) , James A. W. Stowell (MRC Laboratory of Molecular Biology) , Chris H. Hill (MRC Laboratory of Molecular Biology) , Lori Passmore (MRC Laboratory of Molecular Biology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Structural & Molecular Biology , VOL 2

State: Published (Approved)
Published: May 2019
Diamond Proposal Number(s): 15916

Abstract: The 3′ poly(A) tail of messenger RNA is fundamental to regulating eukaryotic gene expression. Shortening of the poly(A) tail, termed deadenylation, reduces transcript stability and inhibits translation. Nonetheless, the mechanism for poly(A) recognition by the conserved deadenylase complexes Pan2–Pan3 and Ccr4–Not is poorly understood. Here we provide a model for poly(A) RNA recognition by two DEDD-family deadenylase enzymes, Pan2 and the Ccr4–Not nuclease Caf1. Crystal structures of Saccharomyces cerevisiae Pan2 in complex with RNA show that, surprisingly, Pan2 does not form canonical base-specific contacts. Instead, it recognizes the intrinsic stacked, helical conformation of poly(A) RNA. Using a fully reconstituted biochemical system, we show that disruption of this structure—for example, by incorporation of guanosine into poly(A)—inhibits deadenylation by both Pan2 and Caf1. Together, these data establish a paradigm for specific recognition of the conformation of poly(A) RNA by proteins that regulate gene expression.

Journal Keywords: RNA metabolism; X-ray crystallography

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Added On: 22/05/2019 12:05

Discipline Tags:

Biochemistry Chemistry Structural biology Biophysics Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)