| Structural highlights
Function
[RED1_RAT] Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2 and GRIK2) and serotonin (HTR2C), GABA receptor (GABRA3) and potassium voltage-gated channel (KCNA1). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alter their functional activities. Edits GRIA2 at both the Q/R and R/G sites efficiently but converts the adenosine in hotspot1 much less efficiently (By similarity). Can inhibit cell proliferation and migration and can stimulate exocytosis.[1] [2] [3]
Publication Abstract from PubMed
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.
The solution structure of the ADAR2 dsRBM-RNA complex reveals a sequence-specific readout of the minor groove.,Stefl R, Oberstrass FC, Hood JL, Jourdan M, Zimmermann M, Skrisovska L, Maris C, Peng L, Hofr C, Emeson RB, Allain FH Cell. 2010 Oct 15;143(2):225-37. PMID:20946981[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yang L, Zhao L, Gan Z, He Z, Xu J, Gao X, Wang X, Han W, Chen L, Xu T, Li W, Liu Y. Deficiency in RNA editing enzyme ADAR2 impairs regulated exocytosis. FASEB J. 2010 Oct;24(10):3720-32. doi: 10.1096/fj.09-152363. Epub 2010 May 25. PMID:20501795 doi:http://dx.doi.org/10.1096/fj.09-152363
- ↑ Stefl R, Xu M, Skrisovska L, Emeson RB, Allain FH. Structure and specific RNA binding of ADAR2 double-stranded RNA binding motifs. Structure. 2006 Feb;14(2):345-55. PMID:16472753 doi:10.1016/j.str.2005.11.013
- ↑ Stefl R, Oberstrass FC, Hood JL, Jourdan M, Zimmermann M, Skrisovska L, Maris C, Peng L, Hofr C, Emeson RB, Allain FH. The solution structure of the ADAR2 dsRBM-RNA complex reveals a sequence-specific readout of the minor groove. Cell. 2010 Oct 15;143(2):225-37. PMID:20946981 doi:10.1016/j.cell.2010.09.026
- ↑ Stefl R, Oberstrass FC, Hood JL, Jourdan M, Zimmermann M, Skrisovska L, Maris C, Peng L, Hofr C, Emeson RB, Allain FH. The solution structure of the ADAR2 dsRBM-RNA complex reveals a sequence-specific readout of the minor groove. Cell. 2010 Oct 15;143(2):225-37. PMID:20946981 doi:10.1016/j.cell.2010.09.026
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