Disease relevance of RNA Editing

• ADAR2-dependent RNA editing of AMPA receptor subunit GluR2 determines vulnerability of neurons in forebrain ischemia [1].
• Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism [2].
• Bacteriophage T4 RNA ligase (gp63) is the best-studied member of this class of enzymes, which includes yeast tRNA ligase and trypanosome RNA-editing ligases [3].
• A recent report showing induction of DNA mutations in Escherichia coli by overexpression of AID, Apobec-1, and related members of the RNA-editing cytidine deaminase family suggested that they may directly modify deoxycytidine in DNA in mammalian cells (DNA-editing model) [4].
• Reduction of GluR2 RNA editing, a molecular change that increases calcium influx through AMPA receptors, selective in the spinal ventral gray of patients with amyotrophic lateral sclerosis [5].

Psychiatry related information on RNA Editing

• Conversion of the codon for glutamine621 to arginine (Q621R) by RNA editing reduces conductance by more than 35-fold to less than 0.4 pS without changing response time course, desensitization, or Po,peak [6].
• Here we examined RNA editing efficiencies of site A and D of HTR2C in the prefrontal cortex samples of patients with bipolar disorder, schizophrenia, and major depression as well as control subjects by using primer extension combined with denaturing high performance liquid chromatography [7].

High impact information on RNA Editing

• RNA editing by adenosine deaminases that act on RNA [8].
• A functionally critical position (Q/R site) of the AMPA receptor subunit GluR-B is controlled by RNA editing that operates in the nucleus, since in brain and clonal cell lines of neural origin, unspliced GluR-B transcripts occur edited in the Q/R site CAG codon and, additionally, in intronic adenosines [9].
• RNA editing occurs at sites asymmetrically distributed along the wheat nad1 coding region, and the initiation codon is created by RNA editing [10].
• RNA editing in brain controls a determinant of ion flow in glutamate-gated channels [11].
• Two RNA editing events in the trans-splicing intron a/b improve conservation of the secondary structure in the stem of domain VI [12].

Chemical compound and disease context of RNA Editing

• RNA editing of glutamate receptor subunits GluR2, GluR5 and GluR6 in transient cerebral ischemia in the rat [13].
• Adenovirus VAI RNA antagonizes the RNA-editing activity of the ADAR adenosine deaminase [14].

Biological context of RNA Editing

• These results suggest that the creation of new amino acid sequences and methionine initiation codons may be important functions of RNA editing in the kinetoplastid mitochondrion [15].
• The shorter form, apo B48, arises by posttranscriptional RNA editing whereby cytidine deamination produces a UAA termination codon [16].
• Alternatively, AID functions like its closest homologue Apobec1 as a catalytic subunit of a RNA editing holoenzyme ('RNA-substrate model') [17].
• The sequence, expression, and RNA editing of the wheat mitochondrial transcription unit containing four open reading frames (nad3, rps12, orf299, orf156), all cotranscribed into a same predominant precursor RNA, have been studied [18].
• Because fully edited, partially edited, and unedited transcripts were found among the cloned polyadenylated cox2 cDNAs, we conclude that RNA editing and polyadenylation are independent processes in maize mitochondria [19].
• A-to-I RNA editing is frequent in human more there any other organism, mostly because of high prevalence of inverted Alu repeats in human genome (more than 10% of the human genome contains Alu repeats) [20].

Anatomical [21] context of RNA Editing

• A full-length complementary DNA clone encoding an apo B messenger RNA editing protein (REPR) was isolated from rat small intestine [16].
• Using an interspecific protoplast fusion approach, we were able to restore RNA editing activity for a specific site in the psbF transcript that otherwise remained unedited [22].
• Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells [23].
• Splicing and intron-internal RNA editing of trnK-matK transcripts in barley plastids: support for MatK as an essential splice factor [24].
• Mammalian enterocytes express apolipoprotein (apo)B-48, which is produced after posttranscriptional RNA editing of the nuclear apoB-100 transcript by the catalytic deaminase apobec-1 [25].

Associations of RNA Editing with chemical compounds

• Here we show that transcripts encoding the 2C subtype of serotonin receptor (5-HT(2C)R) undergo RNA editing events in which genomically encoded adenosine residues are converted to inosines by the action of double-stranded RNA adenosine deaminase(s) [26].
• Examples of RNA editing (see ref. 2 for review) include the insertion and deletion of uridine residues in mitochondrial messenger RNAs in kinetoplastid protozoa, the conversion of a cytidine to uridine in mammalian apolipoprotein-B mRNA, and the appearance of two non-templated guanosine residues in a paramyxovirus transcript [27].
• Glutamate receptor RNA editing in vitro by enzymatic conversion of adenosine to inosine [28].
• RNA editing: a mechanism for gRNA-specified uridylate insertion into precursor mRNA [29].
• The mutant was significantly more cytotoxic than wild-type virus, indicating that cytotoxicity caused by GP is down-regulated by the virus through transcriptional RNA editing and expression of sGP [30].

Gene context of RNA Editing

• The mle(napts) RNA helicase mutation in drosophila results in a splicing catastrophe of the para Na+ channel transcript in a region of RNA editing [31].
• Multiple members of the ADAR (adenosine deaminases acting on RNA) gene family are involved in A-to-I RNA editing [32].
• Experiments using recombinant proteins demonstrate that GRY-RBP binds to ACF and inhibits both the binding of ACF to apoB RNA and C to U RNA editing [33].
• However, addition of recombinant CUGBP2 to a reconstituted system demonstrated a dose-dependent inhibition of C to U RNA editing, which was rescued with either apobec-1 or ACF [34].
• Cloning of an Apobec-1-binding protein that also interacts with apolipoprotein B mRNA and evidence for its involvement in RNA editing [35].

Analytical, diagnostic and therapeutic context of RNA Editing

• Molecular cloning of an apolipoprotein B messenger RNA editing protein [16].
• Evidence is presented that REX1 is responsible for deletion of the 3' overhanging Us from the bridged mRNA 5' cleavage fragment and that RNA editing ligase 1 is responsible for the ligation of the two mRNA cleavage fragments in U-deletion editing [36].
• To determine whether C-to-U type RNA editing restores conventional A-U pairing, we sequenced RT-PCR products from partially-spliced nad7 template RNA and gel-fractionated, excised intron RNA [37].
• DNA translation frames can be disrupted for several reasons, including: (i) errors in sequence determination; (ii) RNA processing, such as intron removal and guide RNA editing; (iii) less commonly, polymerase frameshifting during transcription or ribosomal frameshifting during translation [38].
• These results demonstrate that RNA editing decreases 5-HT2C receptor basal activity, agonist affinity, and potency, indicating that RNA editing may play a role in regulating serotonergic signal transduction and response to drug therapy [39].

References