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Results for “RNA Editing”

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PubMed1991

The wheat mitochondrial gene for subunit I of the NADH dehydrogenase complex: a trans-splicing model for this gene-in-pieces.

The nad1 gene encoding subunit I of the respiratory chain NADH dehydrogenase is fragmented into five unique-copy coding segments that are scattered over at least 40 kb and interspersed with other genes in the wheat mitochondrial genome. The nad1 segments are flanked by sequences with group II intron features, and transcript analysis demonstrates the presence of correctly spliced mRNAs. RNA editing occurs at sites asymmetrically distributed along the wheat nad1 coding region, and the initiation codon is created by RNA editing. The unusual organization of the wheat nad1 gene is attributed to mitochondrial DNA rearrangements within introns, and a trans-splicing model involving secondary structural interactions between group II-like intron pieces is proposed for its expression.

Amino Acid Sequence↗

PubMed2000

Larger intercellular variation in (Q/R) editing of GluR6 than GluR5 revealed by single cell RT-PCR.

RNA editing of the pre-mRNA encoding the kainate receptor subtypes determines the Ca2+ permeability and the rectifying properties of the receptors in which these are assembled. GluR6 pre-mRNA contains three characterized editing sites: Q/R, IN and the Y/C, whereas GluR5 pre-mRNA contains only the (Q/R) site. Single cell RT-PCR was used on cultured cortical neurons to determine the relative expression and editing levels of the kainate receptor subunits encoding mRNA. The analysis showed a large intercellular variation in editing efficiency. The overall lower level of GluR5 editing, in the culture, compared to GluR6 editing is a result of an approximately 60% lower editing efficiency of GluR5 pre-mRNA, within single cells, compared with GluR6.

Animals↗

PubMed1990

Addition of uridines to edited RNAs in trypanosome mitochondria occurs independently of transcription.

RNA editing is a novel RNA processing event of unknown mechanism that results in the introduction of nucleotides not encoded in the DNA into specific RNA molecules. We have examined the post-transcriptional addition of nucleotides into the mitochondrial RNA of Trypanosoma brucei. Utilizing an isolated organelle system we have determined that addition of uridines to edited RNAs does not require ongoing transcription. Trypanosome mitochondria incorporate CTP, ATP, and UTP into RNA in the absence of transcription. GTP is incorporated into RNA only as a result of the transcription process. Post-transcriptional CTP and ATP incorporation can be ascribed to known enzymatic activities. CTP is incorporated into tRNAs as a result of synthesis or turnover of their 3' CCA sequences. ATP is incorporated into the 3' CCA of tRNAs and into mitochondrial messenger RNAs due to polyadenylation. In the absence of transcription, UTP is incorporated into transcripts known to undergo editing, and the degree of UTP incorporation is consistent with the degree of editing occurring in these transcripts. Cytochrome b mRNAs, which contain a single editing site near their 5' ends, are initially transcribed unedited at that site. Post-transcriptional labeling of cytochrome b mRNAs in the organelle with [alpha-32P]UTP results in the addition of uridines near the 5' end of the RNA but not in a 3' region which lacks an editing site. These results indicate that RNA editing is a post-transcriptional process in the mitochondria of trypanosomes.

Adenosine Triphosphate↗

PubMed2006

Alternative editing of cytochrome c oxidase III mRNA in trypanosome mitochondria generates protein diversity.

Trypanosomes use RNA editing to produce most functional mitochondrial messenger RNA. Precise insertion and deletion of hundreds of uridines is necessary to make full-length cytochrome c oxidase III (COXIII) mRNA. We show that COXIII mRNA can be alternatively edited by a mechanism using an alternative guide RNA to make a stable mRNA. This alternatively edited mRNA is translated to produce a unique protein that fractionates with mitochondrial membranes and colocalizes with mitochondrial proteins in situ. Alternative RNA editing represents a previously unknown mechanism generating protein diversity and, as such, represents an important function for RNA editing.

Amino Acid Sequence↗

PubMed1999

Left-handed Z-DNA: structure and function.

Z-DNA is a high energy conformer of B-DNA that forms in vivo during transcription as a result of torsional strain generated by a moving polymerase. An understanding of the biological role of Z-DNA has advanced with the discovery that the RNA editing enzyme double-stranded RNA adenosine deaminase type I (ADAR1) has motifs specific for the Z-DNA conformation. Editing by ADAR1 requires a double-stranded RNA substrate. In the cases known, the substrate is formed by folding an intron back onto the exon that is targeted for modification. The use of introns to direct processing of exons requires that editing occurs before splicing. Recognition of Z-DNA by ADAR1 may allow editing of nascent transcripts to be initiated immediately after transcription, ensuring that editing and splicing are performed in the correct sequence. Structural characterization of the Z-DNA binding domain indicates that it belongs to the winged helix-turn-helix class of proteins and is similar to the globular domain of histone-H5.

Adenosine Deaminase↗

PubMed2005

Editing efficiency of a Drosophila gene correlates with a distant splice site selection.

RNA editing and alternative splicing are two processes that increase protein diversity. The relationship between the two processes is not well understood. There are a few examples of correlations between editing and alternative splicing, but these are all nearby effects. A search for alternative splicing among 16 edited genes in Drosophila reveals two novel instances of alternative splicing. In one example where alternative splicing occurs downstream of editing, a strong correlation between editing efficiency and splice site selection is observed. In contrast, when editing occurs downstream of alternative splicing, no correlation is seen. These results suggest some models for the coupling of editing and splicing processes.

Alternative Splicing↗

PubMed1999

Long RNA hairpins that contain inosine are present in Caenorhabditis elegans poly(A)+ RNA.

Adenosine deaminases that act on RNA (ADARs) are RNA-editing enzymes that convert adenosine to inosine within double-stranded RNA. In the 12 years since the discovery of ADARs only a few natural substrates have been identified. These substrates were found by chance, when genomically encoded adenosines were identified as guanosines in cDNAs. To advance our understanding of the biological roles of ADARs, we developed a method for systematically identifying ADAR substrates. In our first application of the method, we identified five additional substrates in Caenorhabditis elegans. Four of those substrates are mRNAs edited in untranslated regions, and one is a noncoding RNA edited throughout its length. The edited regions are predicted to form long hairpin structures, and one of the RNAs encodes POP-1, a protein involved in cell fate decisions.

3' Untranslated Regions↗

PubMed1990

Characterization of the apolipoprotein B mRNA editing activity in enterocyte extracts.

Apolipoprotein B (apoB) circulates in human plasma as two isoforms, apoB-100 (512 kDa) and apoB-48 (242 kDa). ApoB-48 is generated by a novel RNA editing mechanism which post-transcriptionally modifies apoB mRNA in the intestine by converting cytidine at nucleotide 6666 to uridine. This converts codon 2153 from glutamine (CAA) to a premature stop codon (UAA). To characterize the activity which edits apoB mRNA, extracts were prepared from enterocytes isolated from baboon small intestine. These extracts efficiently edit synthetic apoB RNA in vitro. Editing was detected by primer extension, and the specificity of the reaction was confirmed by DNA sequencing. Extracts prepared from other baboon tissues did not edit apoB RNA in vitro. The editing activity was partially purified by chromatography of the enterocyte extracts on DEAE-cellulose. The activity is sensitive to proteinase K but resistant to micrococcal nuclease and has an average molecular mass of 125 kDa when analyzed by gel filtration chromatography.

Animals↗

PubMed2000

In vitro analysis of the binding of ADAR2 to the pre-mRNA encoding the GluR-B R/G site.

The ADAR family of RNA-editing enzymes deaminates adenosines within RNA that is completely or largely double stranded. In mammals, most of the characterized substrates encode receptors involved in neurotransmission, and these substrates are thought to be targeted by the mammalian enzymes ADAR1 and ADAR2. Although some ADAR substrates are deaminated very promiscuously, mammalian glutamate receptor B (gluR-B) pre-mRNA is deaminated at a few specific adenosines. Like most double-stranded RNA (dsRNA) binding proteins, ADARs bind to many different sequences, but few studies have directly measured and compared binding affinities. We have attempted to determine if ADAR deamination specificity occurs because the enzymes bind to targeted regions with higher affinities. To explore this question we studied binding of rat ADAR2 to a region of rat gluR-B pre-mRNA that contains the R/G editing site, and compared a wild-type molecule with one containing mutations that decreased R/G site editing. Although binding affinity to the two sequences was almost identical, footprinting studies indicate ADAR2 binds to the wild-type RNA at a discrete region surrounding the editing site, whereas binding to the mutant appeared nonspecific.

Adenosine Deaminase↗

PubMed2001

The many roles of an RNA editor.

The availability of complete genome sequences has made it clear that gene number is not the sole determinant of the complexity of the proteome. Additional complexity that is not readily detected by genome analysis is present in the number and types of RNA transcript that can be derived from each locus. Although alternative splicing is a well-recognized method of generating diversity, the more subtle mechanism of RNA editing is less familiar.

Animals↗

PubMed1991

Trans splicing integrates an exon of 22 nucleotides into the nad5 mRNA in higher plant mitochondria.

The genes coding for NADH dehydrogenase subunit 5 (nad5) in mitochondria of the higher plants Oenothera and Arabidopsis are split into five exons that are located in three distant genomic regions. These encode exons a + b, c and d + e, respectively. Maturation of the mRNAs requires two trans splicing events to integrate exon c of only 22 nucleotides. Both trans splicing reactions involve mitochondrial group II intron sequences that allow base pairings in the interrupted domain IV, demonstrating the flexibility of intron structures. The observation of fragmented intron sequences in plant mitochondria suggests that trans splicing is more widespread than previously assumed. RNA editing by C to U alterations in both Oenothera and Arabidopsis open reading frames improves the evolutionary conservation of the encoded polypeptides. Three C to U RNA editing events were observed in intron sequences.

Amino Acid Sequence↗

PubMed2001

The complete DNA sequence of the mitochondrial genome of Physarum polycephalum.

The complete sequence of the mitochondrial DNA (mtDNA) of the true slime mold Physarun polycephalum has been determined. The mtDNA is a circular 62,862-bp molecule with an A+T content of 74.1%. A search with the program BLAST X identified the protein-coding regions. The mitochondrial genome of P. polycephalum was predicted to contain genes coding for 12 known proteins [for three cytochrome c oxidase subunits, apocytochrome b, two F1Fo-ATPase subunits, five NADH dehydrogenase (nad) subunits, and one ribosomal protein], two rRNA genes, and five tRNA genes. However, the predicted ORFs are not all in the same frame, because mitochondrial RNA in P. polycephalum undergoes RNA editing to produce functional RNAs. The nucleotide sequence of an nad7 cDNA showed that 51 nucleotides were inserted at 46 sites in the mRNA. No guide RNA-like sequences were observed in the mtDNA of P. polycephalum. Comparison with reported Physarum mtDNA sequences suggested that sites of RNA editing vary among strains. In the Physarum mtDNA, 20 ORFs of over 300 nucleotides were found and ORFs 14 19 are transcribed.

Amino Acid Sequence↗

PubMed1994

Editing of Trypanosoma brucei maxicircle CR5 mRNA generates variable carboxy terminal predicted protein sequences.

RNA editing post-transcriptionally modifies several mRNAs from the maxicircle of kinetoplastid parasites by addition and removal of uridine residues. We report here that maxicircle CR5 transcripts of Trypanosoma brucei are edited in two domains separated by an eight nucleotide sequence that remains unedited. The large 5' domain is edited to a consensus sequence while the smaller 3' domain is edited to multiple final sequences. In all, 205-217 Us are inserted and 13-16 encoded uridines are deleted from the CR5 mRNA, producing a mature transcript 75-80% larger than the unedited transcript. The edited RNAs predict small, highly hydrophobic proteins. The carboxy terminal 15-30% of these predicted proteins have multiple different amino acid sequences as a result of the variable edited 3' mRNA sequence, but these fall into two families of sequence. Limited amino acid sequence and hydrophobicity profile similarities suggest that the protein encoded by edited CR5 mRNA may be a subunit of NADH dehydrogenase.

Amino Acid Sequence↗

PubMed1996

Editing of GluR2 RNA in the gerbil hippocampus after global cerebral ischemia.

Postischemic delayed neuronal death (DND) in CA1 of the gerbil hippocampus is thought to be caused by an abnormal increase of Ca2+ influx into the cell, mediated by excessive activation of glutamate receptors. One subtype of glutamate receptors, the AMPA receptor, is not permeable to calcium ions as long as an edited form of its GluR2 subunit is present. It is possible that global ischemia interferes with the posttranscriptional editing of the GluR2 mRNA and thus leads to calcium influx via the AMPA receptor. In order to test this hypothesis, we examined the extent of GluR2 RNA editing in CA1 and CA3 microdissected from gerbil hippocampus after 5 min of global ischemia and various recirculation intervals. At each interval tested, quality and quantity of mRNA editing in the vulnerable CA1 region were the same as in CA3. Furthermore, postischemic mRNA editing in both hippocampal regions was indistinguishable from editing in untreated control animals. Our results clearly demonstrate that global ischemia does not cause impairment of GluR2 RNA editing, which is thus not responsible for the abnormal calcium permeability of the postischemic cell membrane.

Animals↗

PubMed1998

Insertional editing of mitochondrial tRNAs of Physarum polycephalum and Didymium nigripes.

tRNAs encoded on the mitochondrial DNA of Physarum polycephalum and Didymium nigripes require insertional editing for their maturation. Editing consists of the specific insertion of a single cytidine or uridine relative to the mitochondrial DNA sequence encoding the tRNA. Editing sites are at 14 different locations in nine tRNAs. Cytidine insertion sites can be located in any of the four stems of the tRNA cloverleaf and usually create a G. C base pair. Uridine insertions have been identified in the T loop of tRNALys from Didymium and tRNAGlu from Physarum. In both tRNAs, the insertion creates the GUUC sequence, which is converted to GTPsiC (Psi = pseudouridine) in most tRNAs. This type of tRNA editing is different from other, previously described types of tRNA editing and resembles the mRNA and rRNA editing in Physarum and Didymium. Analogous tRNAs in Physarum and Didymium have editing sites at different locations, indicating that editing sites have been lost, gained, or both since the divergence of Physarum and Didymium. Although cDNAs derived from single tRNAs are generally fully edited, cDNAs derived from unprocessed polycistronic tRNA precursors often lack some of the editing site insertions. This enrichment of partially edited sequences in unprocessed tRNAs may indicate that editing is required for tRNA processing or at least that RNA editing occurs as an early event in tRNA synthesis.

Animals↗

PubMed2001

A novel orfB-related gene of carrot mitochondrial genomes that is associated with homeotic cytoplasmic male sterility (CMS).

Three types of orfB-related genes, orfB-F1, orfB-F2 and orfB-CMS, were found in carrot mitochondrial genomes. OrfB-F1 has a structure similar to the reported orfB gene in sunflower, and orfB-F2 is a novel chimeric gene with about 200 bp of unknown sequence at the 3' end of the orfB-related sequence. All fertile plants examined contained either orfB-F1 or orfB-F2. OrfB-CMS is also a novel chimeric orfB-related gene with an additional 170 bp of unknown sequence at the 3' end. Fifteen carrot lines including petaloid CMS were examined by PCR analysis and all petaloid CMS plants were found to contain the orfB-CMS gene. The orfB-F2 and orfB-CMS genes coexist in three lines, and these lines exhibit a CMS phenotype, suggesting that the CMS phenotype is associated with orfB-CMS and is independent of the presence of orfB-F2. Interestingly, differences in predicted amino acid sequence between orfB-CMS and orfB-F2 were very limited and restricted to the carboxy-terminal region of the protein. The orfB-related genes were transcribed as expected from their DNA structures, but orfB-CMS protein accumulated only in floral organs of the CMS lines. Four RNA editing sites were common to orfB-CMS and orfB-F2, and C-to-U editing occurred in both floral and leaf organs for orfB-CMS. These results strongly suggest that the orfB-CMS gene is closely associated with the petaloid phenotype and its expression is not regulated by RNA editing, but by post-transcriptional events.

Amino Acid Sequence↗

PubMed1993

Identification and simulation of new non-random statistical properties common to different eukaryotic gene subpopulations.

The nucleotide distribution in protein coding genes, introns and transfer RNA genes of eukaryotic subpopulations (primates, rodent and mammals) is studied by autocorrelation functions. The autocorrelation function analysing the occurrence probability of the i-motif YRY(N)iYRY (YRY-function) in protein coding genes and transfer RNA genes of these three eukaryotic subpopulations retrieves the preferential occurrence of YRY(N)6YRY (R = purine = adenine or guanine, Y = pyrimidine = cytosine or thymine, N = R or Y). The autocorrelation functions analysing the occurrence probability of the i-motifs RRR(N)iRRR (RRR-function) and YYY(N)iYYY (YYY-function) identify new non-random genetic statistical properties in these three eukaryotic subpopulations, mainly: i) in their protein coding genes: local maxima for i identical to 6 [12] (peaks for i = 6, 18, 30, 42) with the RRR-function and local maxima for i identical to 8 [10] (peaks for i = 8, 18, 28) with the YYY-function; and ii) in their introns: local maxima for i identical to 3 [6] (peaks for i = 3, 9, 15) and a short linear decrease followed by a large exponential decrease both with the RRR- and YYY-functions. The non-random properties identified in eukaryotic intron subpopulations are modelised with a process of random insertions and deletions of nucleotides simulating the RNA editing.

Animals↗

PubMed1997

A heterologous maize rpoB editing site is recognized by transgenic tobacco chloroplasts.

Single nucleotides in plant chloroplast transcripts are edited from the genomically encoded C to U, often resulting in changes of the encoded protein sequence. Site-specific trans-acting factors are postulated to direct the selection of edited residues. In order to further define cis sequences required for RNA editing, we investigated whether two editing sites present in maize rpoB mRNA would be recognized by the editing machinery of transformed tobacco chloroplasts. A 93-nucleotide (nt) segment surrounding site I is sufficient to direct editing of the maize sequence in tobacco chloroplasts. However, an 86-nt segment surrounding maize site IV (which is genomically encoded as a T in tobacco) does not confer editing of this site, suggesting that trans-acting factors necessary for recognition of site IV are not present in tobacco. The maize sequences surrounding site I were found to compete with the endogenous rpoB for a depletable trans factor and to reduce editing of endogenous site I. The presence of exogenous maize site I was also found to decrease editing of endogenous tobacco site II, indicating that there is a shared aspect of editing for some closely spaced editing sites.

Base Sequence↗