Cell
Volume 143, Issue 2, 15 October 2010, Pages 225-237
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Article
The Solution Structure of the ADAR2 dsRBM-RNA Complex Reveals a Sequence-Specific Readout of the Minor Groove

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Summary

Sequence-dependent recognition of dsDNA-binding proteins is well understood, yet sequence-specific recognition of dsRNA by proteins remains largely unknown, despite their importance in RNA maturation pathways. Adenosine deaminases that act on RNA (ADARs) recode genomic information by the site-selective deamination of adenosine. Here, we report the solution structure of the ADAR2 double-stranded RNA-binding motifs (dsRBMs) bound to a stem-loop pre-mRNA encoding the R/G editing site of GluR-2. The structure provides a molecular basis for how dsRBMs recognize the shape, and also more surprisingly, the sequence of the dsRNA. The unexpected direct readout of the RNA primary sequence by dsRBMs is achieved via the minor groove of the dsRNA and this recognition is critical for both editing and binding affinity at the R/G site of GluR-2. More generally, our findings suggest a solution to the sequence-specific paradox faced by many dsRBM-containing proteins that are involved in post-transcriptional regulation of gene expression.

Highlights

► The 50 kDa NMR structure of the two dsRBMs of ADAR2 bound to a 71 nt RNA ► Shape and sequence recognition of dsRNA by ADAR2 dsRBMs ► Importance of base-specific contacts for accurate substrate selection by ADAR2 ► Other dsRBMs may operate as sequence-specific RNA binding modules

RNA
PROTEINS

Cited by (0)

6

These authors contributed equally to this work

7

Present address: Department of Bioengineering, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA

8

Present address: Departement de Chimie Moleculaire, 38041 Grenoble Cedex09, France