The Solution Structure of the ADAR2 dsRBM-RNA Complex Reveals a Sequence-Specific Readout of the Minor Groove

ŠTEFL, Richard, Florian OBERSTRASS, Jeniffer HOOD, Muriel JOURDAN, Michal ZIMMERMANN, Lenka SKŘÍŠOVSKÁ, Christophe MARIS, Li PENG, Ctirad HOFR, Ronald EMESON and Frederic ALLAIN. The Solution Structure of the ADAR2 dsRBM-RNA Complex Reveals a Sequence-Specific Readout of the Minor Groove. CELL. UNITED STATES: CELL PRESS, 2010, vol. 143, No 2, p. 225-237. ISSN 0092-8674.

Basic information

• Original name: The Solution Structure of the ADAR2 dsRBM-RNA Complex Reveals a Sequence-Specific Readout of the Minor Groove
• Name in Czech: The Solution Structure of the ADAR2 dsRBM-RNA Complex Reveals a Sequence-Specific Readout of the Minor Groove
• Authors: ŠTEFL, Richard (203 Czech Republic, guarantor, belonging to the institution), Florian OBERSTRASS (756 Switzerland), Jeniffer HOOD (840 United States of America), Muriel JOURDAN (250 France), Michal ZIMMERMANN (203 Czech Republic, belonging to the institution), Lenka SKŘÍŠOVSKÁ (203 Czech Republic), Christophe MARIS (250 France), Li PENG (840 United States of America), Ctirad HOFR (203 Czech Republic, belonging to the institution), Ronald EMESON (840 United States of America) and Frederic ALLAIN (250 France).
• Edition: CELL, UNITED STATES, CELL PRESS, 2010, 0092-8674.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10600 1.6 Biological sciences
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 32.406
• RIV identification code: RIV/00216224:14310/10:00040623
• Organization unit: Faculty of Science
• UT WoS: 000283052200012
• Keywords (in Czech): OUBLE-STRANDED-RNA; TORSION ANGLE DYNAMICS; DSRNA-BINDING DOMAIN; ADENOSINE DEAMINASES; RIBONUCLEASE-III; EDITING ENZYME; PROTEIN-KINASE; GLUR-B; NMR; RECOGNITION
• Keywords in English: OUBLE-STRANDED-RNA; TORSION ANGLE DYNAMICS; DSRNA-BINDING DOMAIN; ADENOSINE DEAMINASES; RIBONUCLEASE-III; EDITING ENZYME; PROTEIN-KINASE; GLUR-B; NMR; RECOGNITION
• Tags: Reviewed

Abstract

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.

Abstract (in Czech)

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.

Links

• GAP305/10/1490, research and development project: Name: Strukturní podstata ukončení transkripce nezávislé na poly(A) signálu

Investor: Czech Science Foundation

• GA204/08/1212, research and development project: Name: Strukturní studium interakcí mezi proteiny a RNA účastnící se v mechanismu kontroly kvality RNA

Investor: Czech Science Foundation, Structural studies of protein-RNA complexes involved in RNA quality control

• GD204/08/H054, research and development project: Name: Molekulární mechanismy proliferace a diferenciace buněk

Investor: Czech Science Foundation, Molecular mechanisms of the cell proliferation and differentiation

• IAA401630903, research and development project: Name: Strukturní podstata mechanismu ukončení transkripce nepolyadenylovaných transkriptů

Investor: Academy of Sciences of the Czech Republic, Structural basis for transcription termination of nonpolyadenylated transcripts

• LA08008, research and development project: Name: Strukturní studium interakcí mezi bíkovinami a poškozenou RNA.

Investor: Ministry of Education, Youth and Sports of the CR, Structural studies of protein-RNA complexes involved in RNA quality control

• MSM0021622413, plan (intention): Name: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministry of Education, Youth and Sports of the CR, Proteins in metabolism and interaction of organisms with the environment

• MSM0021622415, plan (intention): Name: Molekulární podstata buněčných a tkáňových regulací

Investor: Ministry of Education, Youth and Sports of the CR, Molecular basis of cell and tissue regulations