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PubMed2006

Divergent RNA editing frequencies in hornwort mitochondrial nad5 sequences.

Hornwort mitochondrial genomes have some of the highest rates of RNA editing among plants. Comparison of eleven partial mitochondrial nad5 genomic and cDNA sequences from diverse taxa of hornworts reveal 125 edited sites in only 1107 nt. No single sample exhibits more than half of these sites. Ten of the 11 hornwort taxa have between 35 and 54 edited sties each; whereas, the eleventh taxon, Leiosporoceros, which represents a potential sister taxa to all other hornworts, has only eight sites. Comparison of multiple cDNA sequences from several individuals reveals the presence of many immature transcripts showing the heterogonous nature of the progression of editing. Phylogenetic analyses of hornwort genomic and cDNAs sequences reveal that 65 of the 94 phylogenetically informative sites within the hornwort clade are edited positions.

Anthocerotophyta↗

PubMed2006

C6-substituted analogues of 8-azanebularine: probes of an RNA-editing enzyme active site.

[reaction: see text] We describe the synthesis of derivatives of 8-azanebularine, a known inhibitor of adenosine deaminases including the RNA-editing enzyme ADAR2. 6-Methyl, 6-hydroxymethyl, 6-cyano, and 6-mercapto derivatives were obtained from 6-bromo precursors using different cross-coupling or substitution reactions. The C6-methyl derivative was incorporated into an RNA substrate for ADAR2 via the phosphoramidite. Quantitative gel mobility shift experiments with the resulting RNA indicate that methylation at C6 dramatically reduces the affinity of 8-azanebularine for ADAR2.

Adenosine Deaminase↗

PubMed1998

Translation of tobacco chloroplast rps14 mRNA depends on a Shine-Dalgarno-like sequence in the 5'-untranslated region but not on internal RNA editing in the coding region.

The role of Shine-Dalgarno-like sequences in mRNAs from higher plant chloroplasts has not been analyzed experimentally so far. In vitro translation analysis has revealed that the Shine-Dalgarno-like sequence is essential for translation of tobacco chloroplast rps14 mRNA. Two RNA editing sites have been identified in the protein-coding region of the rps14 mRNA. Editing of the second site was found to be partial and hence the partially edited transcripts are accumulated in tobacco green leaves. In vitro translation assays using the fully edited, partially edited and unedited rps14 mRNAs indicated that editing does not directly influence translational efficiency.

Amino Acid Sequence↗

PubMed1989

RNA editing: the creation of nucleotide sequences in mRNA--a minireview.

RNA editing changes the nucleotide sequence of mRNAs that are encoded in genes which contain the sequences in an abbreviated form. Editing adds uridines that are not encoded in the gene to the transcripts and less frequently removes encoded uridines. The process appears to be posttranscriptional and to proceed in the 3'-to-5' direction. Some sites may undergo multiple editings until the final sequence is produced; in some cases uridines may be added and subsequently removed. A general hypothesis is proposed that predicts a series of reactions that may occur in association with a macromolecular complex, the editosome, which interacts with a multinucleotide region.

Animals↗

PubMed1993

RNA editing of the barley (Hordeum vulgare) mitochondrial ATP synthase subunit 9.

The barley (Hordeum vulgare) FO-ATP synthase subunit 9 (atp9) was isolated from the mitochondrial DNA. Two copies of atp9 are present in barley mitochondria and 2 major transcripts of 2.7 kb and 1.2 kb were detected on RNA blots. RNA editing as C-to-U conversion occurs in barley atp9 in seven positions. Five of these seven positions lead to an amino acid change whereas two conversions are silent. The editing positions of barley were found to be identical to those of wheat. Whereas in wheat, Oenothera and Petunia all the atp9 transcripts were fully edited, 24% of the barley cDNA clones were partially edited as compared to 10% partially edited clones in wheat.

Arabidopsis Proteins↗

PubMed2000

Altered G protein-coupling functions of RNA editing isoform and splicing variant serotonin2C receptors.

Different isoforms of serotonin subtype 2C receptor (5-HT(2C)R) with altered G protein-coupling efficacy are generated by RNA editing, which converts genomically encoded adenosine residues into inosines. In combination, editing of five sites all located within the second intracellular loop region of 5-HT(2C)R mRNA changes the gene-encoded Ile, Asn, and Ile at positions 156, 158, and 160, respectively. We analyzed the G protein-coupling functions of previously unreported editing isoform receptors. An approximately 13-fold reduction in the agonist potency for G protein-coupling stimulation as well as a significantly reduced basal level activity was observed with the thalamus-specific isoform carrying Ile156, Gly158, and Val160 (5-HT(2C)R-IGV). In contrast, the agonist was four- to five-fold less potent with 5-HT(2C)R-MSV and -IDV, detected in the amygdala and choroid plexus, respectively, indicating a dominant role for the amino acid residue at position 158 in receptor functions. We also identified a splicing variant receptor with a truncated C terminus that displayed no ligand binding capacity or G protein-coupling activity. Examination of the alternatively spliced RNA encoding this truncated receptor suggests that editing of this variant RNA occurs after completion of splicing, resulting in complete editing at all five sites.

3T3 Cells↗

PubMedDate not supplied

RNA editing (Q/R site) and flop/flip splicing of AMPA receptor transcripts in young and old brains.

The effects of aging on the efficiency of RNA processing of AMPA glutamate receptor (GluR) subunits GluR1, GluR2, and GluR 3 was examined for RNA editing at the Q/R site of GluR2 and for alternative splicing of the flip or flop exons for GluR1-3. RNA isolated from six young (3 months old) and old (22-23 months old) animals was reverse-transcribed for PCR and restriction endonuclease analyses to distinguish between edited forms of GluR2 and flip/flop isoforms of GluR1-3. Unedited transcripts of GluR2 at the Q/R site (which controls calcium permeability) were not detected (at the limit of detection of >/= 2.5%) from the corticies and hippocampi of young and old animals. Distribution of flop/flip isoforms in the cortex, hippocampus, hypothalamus, and striatum varied between GluR subunits and brain region, with GluR2 showing the greatest differences. However, no differences in alternative splicing of GluRs 1-3 were observed between young and old animals, suggesting that the fidelity of GluR transcript processing remains intact in the brains of aged animals.

Aging↗

PubMed2000

Immunology. RNA editing AIDs antibody diversification?

How do B cells generate the enormous diversity of antibodies that are able to recognize and bind to whichever antigen a B cell might happen to encounter in the body? Several genetic mechanisms that manipulate different combinations of immunoglobulin genes are known. In their Perspective, Neuberger and Scott, highlight another genetic mechanism called RNA editing now shown to be involved in the production of antibody diversity.

APOBEC-1 Deaminase↗

PubMed1994

Molecular characterization of the human EAA5 (GluR7) receptor: a high-affinity kainate receptor with novel potential RNA editing sites.

Several cDNA clones encoding EAA5 receptor polypeptides were isolated from a human fetal brain library. The EAA5 cDNAs demonstrated an 88.7-90.1% nucleotide identity with rat GluR7 cDNAs. The nucleotide sequence of EAA5 would encode a 919-amino acid protein, that has a 97.7-98.9% identity with the rat GluR7 receptor. Two variation of the EAA5 cDNA were identified which result in amino acid substitutions in the predicted extracellular amino-terminal region; Ser310-->Ala and Arg352-->Gln. These variations can be attributed to RNA editing involving T-->G and G-->A substitutions. Both the location (with respect to glutamate receptors), and the nucleotides involved, in this putative RNA editing are novel and may therefore involve novel mechanisms. Ligand binding studies with membranes of transfected COS-1 cells expressing EAA5 polypeptides demonstrate a rank order of ligand affinity similar to that observed with the rat GluR7 receptor, and a dissociation constant for kainate (2.72 +/- 0.12 nM (n = 3)) that is approximately 20- to 30-fold higher than that observed for the rat GluR7 receptor. All of the ligands tested had a higher affinity for the human EAA5 receptor as compared to the rat GluR7 receptor. This report provides another example of pharmacological differences for similar receptors across species.

Amino Acid Sequence↗

PubMed2005

Modulation of microRNA processing and expression through RNA editing by ADAR deaminases.

Adenosine deaminases acting on RNA (ADARs) are involved in editing of adenosine residues to inosine in double-stranded RNA (dsRNA). Although this editing recodes and alters functions of several mammalian genes, its most common targets are noncoding repeat sequences, indicating the involvement of this editing system in currently unknown functions other than recoding of protein sequences. Here we show that specific adenosine residues of certain microRNA (miRNA) precursors are edited by ADAR1 and ADAR2. Editing of pri-miR-142, the precursor of miRNA-142, expressed in hematopoietic tissues, resulted in suppression of its processing by Drosha. The edited pri-miR-142 was degraded by Tudor-SN, a component of RISC and also a ribonuclease specific to inosine-containing dsRNAs. Consequently, mature miRNA-142 expression levels increased substantially in ADAR1 null or ADAR2 null mice. Our results demonstrate a new function of RNA editing in the control of miRNA biogenesis.

Adenosine Deaminase↗

PubMed2000

A novel type of RNA editing occurs in the mitochondrial tRNAs of the centipede Lithobius forficatus.

We determined the complete mtDNA sequence of the centipede Lithobius forficatus and found that only one of the 22 inferred tRNA genes encodes a fully paired aminoacyl acceptor stem. The other 21 genes encode tRNAs with up to five mismatches in these stems, and some of these overlap extensively with the downstream genes. Because a well-paired acceptor stem is required for proper tRNA functioning, RNA editing in the products of these genes was suspected. We investigated this hypothesis by studying cDNA sequences from eight tRNAs and found the editing of up to 5 nt at their 3' ends. This editing appears to occur by a novel mechanism with the 5' end of the acceptor stem being used as a template for the de novo synthesis of the 3' end, presumably by an RNA-dependent RNA polymerase. In addition, unusual secondary structures for several tRNAs were found, including those lacking a TPsiC (T) or a dihydrouridine (D) arm, and having an unusual number of base pairs in the acceptor or anticodon stems.

Animals↗

PubMed1997

Resolution of the RNA editing gRNA-directed endonuclease from two other endonucleases of Trypanosoma brucei mitochondria.

RNA editing in kinetoplastids, the specific insertion and deletion of U residues, requires endonuclease cleavage of the pre-mRNA at each cycle of insertion/deletion. We have resolved three endoribonuclease activities from Trypanosoma brucei mitochondrial extracts that cleave CYb pre-mRNA specifically. One of these, which sediments at approximately 20S and is not affected substantially by DTT, has all the features of the editing endonuclease. It cleaves CYb pre-edited or partially edited mRNA only when annealed to the anchor region of a cognate guide RNA (gRNA), and it cleaves accurately just 5' of the duplex region. Its specificity is for the 5' end of extended duplex RNA regions, and this prevents cleavage of the gRNA or other positions in the mRNA. This gRNA-directed nuclease is evidently the same activity that functions in A6 pre-mRNA editing. However, it is distinct and separable from a previously observed DTT-requiring endonuclease that sediments similarly under certain conditions, but does not cleave precisely at the first editing site in either the presence or absence of a gRNA. The editing nuclease is also distinct from a DTT-inhibited endonuclease that cleaves numerous free pre-mRNAs at a common structure in the region of the first editing site.

Animals↗

PubMed1996

RNA editing of larch mitochondrial tRNA(His) precursors is a prerequisite for processing.

Larch mitochondria contain a'native'tRNAHis which is absent from angiosperms. Sequence comparisons of genomic DNA and cDNA obtained from unprocessed primary transcripts of the larch mitochondrial gene trnH encoding this tRNA revealed three nucleotide discrepancies. These three nucleotide alterations, in the acceptor stem, D stem and anticodon stem respectively, are conversions of genomic cytidines to thymidines in the cDNA (uridines in the tRNA) and thus resemble the RNA editing events observed in nearly all plant mitochondrial mRNAs. Two cases of editing affecting mitochondrial tRNAs from angiosperms have already been described, but we present here the first example of such events in a gymnosperm mitochondrial tRNA. All three editing events correct mismatched C x A base pairs which appear when folding the gene sequence into the standard cloverleaf structure, thereby improving the secondary structure of the tRNA. When incubated with a heterologous potato mitochondrial processing extract, only the edited form of the larch mitochondrial tRNAHis precursor was efficiently processed in vitro. These data strongly suggest that editing of larch mitochondrial tRNAHis is a prerequisite for its processing.

Base Sequence↗

PubMed2005

Mitochondrial electroporation and in organello RNA editing of chimeric atp6 transcripts.

The Sorghum bicolor atp6-1 gene and chimeric atp6 genes with additional maize sequences were introduced into isolated maize mitochondria via electroporation. Transcripts isolated after in vitro incubation of the transformed organelles were then analysed for RNA editing. Transcripts of the S. bicolor atp6-1 gene, and the RNAs obtained from most of chimeric sorghum-maize atp6 gene constructs tested, were not edited. However, the transcript of one engineered chimeric gene comprising the 5'untranslated sequence and a segment of the N-terminal ORF of the maize atp6 combined with the sorghum atp6 core ORF and 3'untranslated sequence was found to be partially edited. We were able to exclude low RNA stability or insufficient editing capacity as the reason for failure to edit in the other instances. Instead, the data indicate that the maize sequence in the edited fusion transcript provides a structural motif or binding site for a transcript-specific editing factor.

Base Sequence↗

PubMed2004

RNA editing and short variant of serotonin 2C receptor mRNA in neuronally differentiated NG108-15 cells.

Two types of serotonin 2C subtype receptor mRNA, receptor-type and short variant, has been reported. The expression of the receptor-type mRNA could be detected as well as the short variant in NG108-15 cells by using a high temperature stable reverse transcriptase and the expression of the receptor-type mRNA was enhanced in drug-induced neuronal differentiated cells. The deleted sequence of the short variant include the RNA editing site by adenosine deaminase. Analysis of the sequence at the editing site revealed that the mRNA of undifferentiated cells was highly edited at sites A and B and that cytosine deaminase activity may also be involved in neuronal differentiation.

Animals↗

PubMed1997

Splicing and intron-internal RNA editing of trnK-matK transcripts in barley plastids: support for MatK as an essential splice factor.

Group II introns frequently require assistance by specific factors, maturases, for folding and effective splicing in vivo. The only putative maturase of higher plant chloroplasts is encoded by matK, located in the intron of trnK. We show that in barley matK transcripts are modified at a first codon base by C-to-U RNA editing. The resulting H --> Y substitution restores a sequence motif that is present in maturases of yeast and plant mitochondria and of Lactococcus ltrA and that is positioned within the X domain. Processing of trnK-matK transcripts was further investigated in plastids lacking functional ribosomes due to a mutation. Absence of the intron-encoded matK gene product in these plastids is correlated with the accumulation of precursor transcripts for tRNALys(UUU)-matK, processed to different degrees, and by the lack of mature and spliced tRNA molecules. These results suggest an essential role of MatK for splicing of its own transcript in vivo. Processing of the 5' end of trnK exon 1 was found to proceed efficiently also in the mutant plastids although the two tRNA exons were separated by the 2481 nt intron. Consequently, presence of the intron does not interfere with the formation of mature 5' termini.

Amino Acid Sequence↗

PubMed1998

Trypanosoma brucei TBRGG1, a mitochondrial oligo(U)-binding protein that co-localizes with an in vitro RNA editing activity.

We report the characterization of a Trypanosoma brucei 75-kDa protein of the RGG (Arg-Gly-Gly) type, termed TBRGG1. Dicistronic and monocistronic transcripts of the TBRGG1 gene were produced by both alternative splicing and polyadenylation. TBRGG1 was found in two or three forms that differ in their electrophoretic mobility on SDS-polyacrylamide gel electrophoresis gels, one of which was more abundant in the procyclic form of the parasite. TBRGG1 was localized to the mitochondrion and appeared to be more abundant in bloodstream intermediate and stumpy forms in which the mitochondrion reactivates and during the procyclic stage, which possesses a fully functional mitochondrion. This protein was characterized to display oligo(U) binding characteristics and was found to co-localize with an in vitro RNA editing activity in a sedimentation analysis. TBRGG1 most likely corresponds to the 83-kDa oligo(U)-binding protein previously identified by UV cross-linking of guide RNA to mitochondrial lysates (Leegwater, P., Speijer, D., and Benne, R. (1995) Eur. J. Biochem. 227, 780-786).

Alternative Splicing↗

PubMed2006

RNA editing complex interactions with a site for full-round U deletion in Trypanosoma brucei.

Trypanosome U insertion and U deletion RNA editing of mitochondrial pre-mRNAs is catalyzed by multisubunit editing complexes as directed by partially complementary guide RNAs. The basic enzymatic activities and protein composition of these high-molecular mass complexes have been under intense study, but their specific protein interactions with functional pre-mRNA/gRNA substrates remains unknown. We show that editing complexes purified through extensive ion-exchange chromatography and immunoprecipitation make specific cross-linking interactions with A6 pre-mRNA containing a single 32P and photoreactive 4-thioU at the scissile bond of a functional site for full-round U deletion. At least four direct protein-RNA contacts are detected at this site by cross-linking. All four interactions are stimulated by unpaired residues just 5' of the pre-mRNA/gRNA anchor duplex, but strongly inhibited by pairing of the editing site region. Furthermore, competition analysis with homologous and heterologous transcripts suggests preferential contacts of the editing complex with the mRNA/gRNA duplex substrate. This apparent structural selectivity suggests that the RNA-protein interactions we observe may be involved in recognition of editing sites and/or catalysis in assembled complexes.

Animals↗