Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The double-stranded RNA-specific editase 1 (RED1/ADAR2) is implicated in the editing of precursor-mRNAs (pre-mRNA) encoding subunits of glutamate receptors (GluRs) in brain. Site-specific deamination of adenosine to inosine alters the codon at the Q/R site in GluR-B rendering the heteromeric receptor impermeable to Ca2+ ions. We cloned human RED1 (hRED1/hADAR2) cDNAs from a brain cDNA library. The human enzyme is 95% identical to the rat homologue. We characterized two alternatively spliced forms that differed by the presence of an Alu-J cassette in the deaminase domain. For the long form containing the Alu cassette, we isolated cDNA clones with an alternative C-terminus and 3'-UTR. An 8.8-kb transcript of hRED1 is most abundant in brain and heart, and lower levels are detected in other tissues. In vitro editing assays with purified recombinant hRED1 containing or lacking the Alu-J cassette revealed that both forms of the protein have the same substrate specificity, but differ in their catalytic activity.
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PMID:Two forms of human double-stranded RNA-specific editase 1 (hRED1) generated by the insertion of an Alu cassette. 914 27

ADAR2 is a member of a family of RNA editing enzymes found in metazoa that bind double helical RNAs and deaminate select adenosines. We find that when human ADAR2 is overexpressed in the budding yeast Saccharomyces cerevisiae it substantially reduces the rate of cell growth. This effect is dependent on the deaminase activity of the enzyme, suggesting yeast transcripts are edited by ADAR2. Characterization of this novel set of RNA substrates provided a unique opportunity to gain insight into ADAR2's site selectivity. We used RNA-Seq. to identify transcripts present in S. cerevisiae subject to ADAR2-catalyzed editing. From this analysis, we identified 17 adenosines present in yeast RNAs that satisfied our criteria for candidate editing sites. Substrates identified include both coding and noncoding RNAs. Subsequent Sanger sequencing of RT-PCR products from yeast total RNA confirmed efficient editing at a subset of the candidate sites including BDF2 mRNA, RL28 intron RNA, HAC1 3'UTR RNA, 25S rRNA, U1 snRNA, and U2 snRNA. Two adenosines within the U1 snRNA sequence not identified as substrates during the original RNA-Seq. screen were shown to be deaminated by ADAR2 during the follow-up analysis. In addition, examination of the RNA sequence surrounding each edited adenosine in this novel group of ADAR2 sites revealed a previously unrecognized sequence preference. Remarkably, rapid deamination at one of these sites (BDF2 mRNA) does not require ADAR2's dsRNA-binding domains (dsRBDs). Human glioma-associated oncogene 1 (GLI1) mRNA is a known ADAR2 substrate with similar flanking sequence and secondary structure to the yeast BDF2 site discovered here. As observed with the BDF2 site, rapid deamination at the GLI1 site does not require ADAR2's dsRBDs.
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PMID:RNA-Seq analysis identifies a novel set of editing substrates for human ADAR2 present in Saccharomyces cerevisiae. 2412 32