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At least 523 records · Page 29Linked to original sources
PubMed1992

Apolipoprotein B messenger RNA editing in rat liver: developmental and hormonal modulation is divergent from apolipoprotein A-IV gene expression despite increased hepatic lipogenesis.

Rat hepatic apolipoprotein B (apoB) mRNA editing is regulated developmentally as well as by hormonal and nutritional modulation of hepatic lipogenesis, changes previously associated with coordinate modulation of hepatic apoA-IV gene expression. We have examined the effects of dexamethasone administration on apoB mRNA editing and the expression of other apolipoprotein genes in both neonatal and adult rats. Administration of dexamethasone increased hepatic triglyceride content in neonatal rats and increased hepatic but not intestinal apoA-IV mRNA abundance. However, neither the developmental profile nor the extent of hepatic apoB mRNA editing was changed after hormone administration. Dexamethasone produced a dose-dependent increase in adult hepatic triglyceride content and a coordinate fourfold increase in hepatic but not intestinal apoA-IV mRNA abundance, and hepatic and serum apoA-IV protein concentrations. Immunocytochemical localization revealed apoA-IV to be expressed in hepatocytes around the central vein while dexamethasone treatment produced a dose-dependent appearance of fat-filled hepatocytes throughout the lobule that were immunoreactive for apoA-IV. Despite these changes in hepatic triglyceride accumulation there was no change in the extent of hepatic apoB mRNA editing at any dose of dexamethasone. The data suggest that hormonal and metabolic modulation of hepatic apoB mRNA editing may be independent of factors that modulate apoA-IV gene expression despite alterations in hepatic triglyceride content.

Animals↗
PubMed1989

Nucleotide sequences of dnaE, the gene for the polymerase subunit of DNA polymerase III in Salmonella typhimurium, and a variant that facilitates growth in the absence of another polymerase subunit.

The dnaE gene of Salmonella typhimurium, like that of Escherichia coli, encodes the alpha subunit containing the polymerase activity of the principal replicative enzyme, DNA polymerase III. This gene, or one nearby, has been identified as the locus of suppressor mutations that promote growth by cells deleted for dnaQ, the gene for the editing subunit of this enzyme complex. Using a combination of nucleotide sequencing and marker rescue experiments, the alteration in one such suppressor was identified as a valine-to-glycine substitution at amino acid 832 of the 1,160-amino-acid alpha polypeptide. The alpha polypeptides of E. coli and S. typhimurium are identical in size and in 97% of their amino acid residues. Their identity includes the valine residue that was changed in the suppressor allele of S. typhimurium. We also localized a temperature-sensitive dnaE mutation to the 3' half of dnaE.

Amino Acid Sequence↗
PubMed1998

Genes for the ribosomal S4 protein encoded in higher plant mitochondria are transcribed, edited, and translated.

Here we describe the structure and expression of the mitochondrial gene that encodes the S4 subunit of the mitochondrial ribosome (rps4) in two higher plants, rapeseed and rice. The ORFs of rapeseed and rice rps4 genes are 362 and 352 codons long, respectively, and their corresponding transcripts are edited (C-to-U conversions) in 19 and 15 positions, respectively. The amino acid sequences deduced from the sequences of the two rps4 genes are 78.1% identical to each other and show about 50% identity to the liverwort (Marchantia polymorpha) mitochondrial RPS4 polypeptide. Both higher plant mitochondrial genes have an inserted sequence (of 137 and 141 codons for rapeseed and rice, respectively) relative to the liverwort rps4 gene. In rice rps4, the 3' portion of the inserted sequence can potentially form two stem-loop structures that resemble two domains characteristic of group II introns, i.e., domains V and VI. However, RT-PCR analysis showed that these sequences were not spliced out during maturation of the rps4 transcripts. Antibodies specific for the plant RPS4 proteins were prepared. Protein blot analysis revealed that RPS4 polypeptides are present in both rapeseed and rice mitochondria, whose sizes are in agreement with the molecular weights calculated from the non-spliced sequences. The rps4 genes and RPS4 polypeptides have been also identified in the mitochondria of wheat, maize, soybean, and turnip by Southern and Western analyses, respectively.

Amino Acid Sequence↗
PubMed2002

Composition of the editing complex of Trypanosoma brucei.

The RNA editing that produces most functional mRNAs in trypanosomes is catalysed by a multiprotein complex. This complex catalyses the endoribonucleolytic cleavage, uridylate addition and removal, and RNA ligation steps of the editing process. Enzymatic and in vitro editing analyses reveal that each catalytic step contributes to the specificity of the editing and, together with the interaction between gRNA and the mRNA, results in precisely edited mRNAs. Tandem mass spectrometric analysis was used to identify the genes for several components of biochemically purified editing complexes. Their identity and presence in the editing complex were confirmed using immunochemical analyses utilizing mAbs specific to the editing complex components. The genes for two RNA ligases were identified. Genetic studies show that some, but not all, of the components of the complex are essential for editing. The TbMP52 RNA ligase is essential for editing while the TbMP48 RNA ligase is not. Editing was found to be essential in bloodstream form trypanosomes. This is surprising because mutants devoid of genes encoding RNAs that become edited survive as bloodstream forms but encouraging since editing complex components may be targets for chemotherapy.

Amino Acid Sequence↗
PubMed2025

Nondestructive Larval Genotyping of Danio rerio for Mitochondrial and Nuclear DNA Genetics.

The rapid advancement of nuclear and mitochondrial genomic editing tools has created an urgent need for efficient, nonlethal larval genotyping methods in zebrafish (Danio rerio) research. This study optimizes and validates a nondestructive proteinase K digestion method for mitochondrial and nuclear DNA genotyping while characterizing its impact on larval survival and gene expression. Using optimized protocol parameters, we demonstrate successful amplification of different mitochondrial and nuclear genetic loci with consistently high sensitivity. Molecular validation through PCR, restriction fragment length polymorphism analysis, and Sanger sequencing confirmed the specificity and reliability of the extracted DNA. The method successfully detected C-to-T base edits in the mt-tl1 gene introduced using the FusX TALE Base editor system, demonstrating its applicability to gene editing studies. Both 48-well and optimized 96-well formats were used, enabling this approach to be deployed at scale. This optimized method enables researchers to correlate genotypes with phenotypes in longitudinal studies while maintaining specimen viability, particularly valuable for investigating early-onset mitochondrial diseases, and utilizes standard laboratory equipment and reagents, facilitating widespread adoption in zebrafish research while adhering to ethical principles in reducing animal mortality.

Animals↗
PubMed1998

Sendai viruses with altered P, V, and W protein expression.

Wild-type Sendai virus expresses three proteins containing the N-terminal half of the P protein open reading frame due to mRNA editing; a full-length P protein (ca. 70% of the total), a V protein with the N-terminal half fused to a Cys-rich Zn(2+)-binding domain (ca. 25% of the total), and a W protein representing the N-terminal half alone (ca. 5% of the total). To examine the role of these proteins in the virus life cycle, we have prepared recombinant viruses in which the normal V mRNA expresses a W protein (V-stop; 70% P, 30% W), one which cannot edit its P gene mRNA (delta 6A; 100% P), and one which overedits its mRNA like parainfluenza virus type 3 (swap/8;20-40% P, 30% V, 30% W). All these viruses were readily recovered and grew to similar titers in eggs, and except for the P gene products, cell lines individually infected with these viruses accumulated similar amounts of viral macromolecules. The relative competitive advantage of each virus was determined by multiple cycle coinfections of eggs and found to be rSeV-Vstop = rSeV-wt >> rSeV-delta 6A > rSeV-swap/8. On the other hand, rSeV-swap/8 underwent multiple cycles of replication in C57BI/6 mouse lungs and was highly virulent for these animals, whereas rSeV-delta 6A was avirulent in mice and this infection was quickly cleared. Remarkably, rSeV-Vstop appeared to be more virulent for inbred C57BI/6 mice than rSeV-wt, but was partially attenuated in infections of outbred ICR mice. Thus, the expression of either the V or the W proteins is sufficient for multiple cycles of infection and pathogenesis in C57BI/6 mice, whereas W can only partially substitute for V for pathogenesis in ICR mice.

Animals↗
PubMed2026

Holistic approaches for improvement of maize resistance against lodging stress: current status and future perspective.

Lodging is a major constraint in maize production, causing significant yield losses, reduced grain quality, and harvesting inefficiencies, thereby posing a serious challenge to global food security and climate-resilient agriculture. This review synthesizes current knowledge on the genetic, physiological, and agronomic determinants of maize lodging resistance and evaluates holistic strategies for improving tolerance to lodging stress. Recent advances in quantitative trait locus (QTL) mapping, genome-wide association studies (GWAS), functional gene characterization, genome editing, high-throughput phenotyping, and precision agronomy have provided powerful tools to enhance stalk biomechanics, root anchorage, and adaptive plant architecture. Integrating genomic discovery with advanced phenomics and optimized agronomic management offers a scalable framework for accelerating the development of high-yielding, lodging-resilient maize cultivars. However, critical gaps remain in understanding the genetic coordination between stalk strength and root system architecture, integrating multi-omics approaches to unravel regulatory networks, validating genome-editing interventions across diverse agro-ecologies, and developing environment-responsive predictive breeding models and cost-effective phenotyping tools, particularly for stress-prone regions. Addressing these challenges through coordinated multi-environment trials and integrative molecular-agronomic strategies will facilitate the translation of genomic discoveries into climate-resilient, high-performing maize cultivars. By consolidating molecular insights with applied breeding and management practices, this review provides a comprehensive framework that guides researchers in designing genome-informed and field-validated approaches to improve maize resistance to lodging stress and support sustainable crop production systems.

Zea mays↗
PubMed2000

Complete sequence of the mitochondrial DNA of the primitive opisthobranch gastropod Pupa strigosa: systematic implication of the genome organization.

The complete sequence (14,189 bp) of the mitochondrial DNA of the opisthobranch gastropod Pupa strigosa was determined. The genome contains 13 protein, 2 rRNA, and 22 tRNA genes typical of metazoan mtDNA. The Pupa mitochondrial genome is highly compact and shows the following unusual features, like pulmonate land snails: (1) extremely small genome size, (2) absence of lengthy noncoding regions (with the largest intergenic spacer being only 46 nt), (3) size reduction of encoded genes, and (4) many overlapping genes. Several tRNA genes exhibit bizarre secondary structures with reduced T or D stems, and many tRNA genes have unstable acceptor stems that might be corrected by posttranscriptional RNA editing. The Pupa mitochondrial gene arrangement is almost identical to those of pulmonate land snails but is radically divergent from those of the prosobranch gastropod Littorina saxatilis and other molluscs. Our finding that the unique gene arrangement and highly compact genome organization are shared between opisthobranch and pulmonate gastropods strongly suggests their close phylogenetic affinity.

Amino Acid Sequence↗
PubMed2003

Analysis of secondary V(D)J rearrangements in mature, peripheral T cells of ataxia-telangiectasia heterozygotes.

Ataxia-telangiectasia (AT) is a rare recessive disease with pleiotropic involvement of the nervous and lymphoid systems. AT heterozygotes have a population frequency of about 1%, and although not manifesting any overt clinical symptoms, they have an increased mortality, mainly because of cancer and ischemic heart disease. We and others have described a mature T lymphocyte population with an altered T cell receptor surface expression ("TCR variant") that reactivates the recombination activating genes (RAG) and is expanded in the blood of patients with AT. In view of the known role of V(D)J recombination in the onset of tumorigenic translocations, we proposed that the increased RAG activity was responsible for the predisposition of AT homozygotes to develop mature-type T leukemia/lymphoma. In the present report, we used cytofluorimetry to quantify the TCR variant population and the memory/naïve T-cell compartments in the blood of AT heterozygotes compared with AT patients and controls. We assessed the expression of different recombinase genes through RT-PCR/oligotyping and cytofluorometric analysis and searched for rearrangement intermediates by ligase-mediated PCR in T-cell lines from four heterozygous carriers. We found the TCR variant population was increased on average 2x in AT heterozygotes (vs 10x in homozygotes) compared with controls, and naïve CD4(+) T lymphocytes were reduced on average 0.5x (vs 0.1x in homozygotes). We were able to demonstrate recombinase gene expression in all four heterozygous T-cell lines, and rearrangement intermediates, indicative of ongoing V(D)J recombination, in two. These rearrangements were compatible with V-gene replacement, a mechanism of receptor editing described for Ig and TCRalpha genes, to our knowledge not previously documented for TCRbeta. In conclusion, we found that RAG reactivation and secondary V(D)J rearrangements, potential risk factors of mature-type leukemia in AT homozygotes, also take place in AT heterozygous carriers and might place this large population fraction at an increased risk of leukemia/lymphoma.

Ataxia Telangiectasia↗
PubMed2026

Hormone priming and metabolic engineering of phytohormone crosstalk in rice under combined biotic and abiotic stresses: a multi-omics perspective for climate-resilient crop development.

Rice (Oryza sativa L.) is the caloric backbone for more than half of humanity, yet it remains one of the most vulnerable crops to the simultaneous biotic and abiotic stresses exacerbated by climate change. Phytohormone priming and the complex crosstalk networks governed by transcription factor hubs like WRKY, MYB, and NAC serve as the central adaptive mechanism for stress resilience. This review synthesizes how multi-omics integration, including spatial and single-cell transcriptomics, is resolving the molecular architecture of hormonal priming and epigenetic stress memory. We critically evaluate advanced metabolic engineering and genome-editing strategies such as CRISPR-Cas9, base/prime editing, and synthetic gene circuits that enable precision modifications to decouple stress tolerance from historical yield penalties. Furthermore, we discuss the emerging roles of microbiome-assisted priming via synthetic consortia and the application of artificial intelligence and digital twins (continuously updated computational models of crop physiology) for predictive stress management. By integrating these diverse technological pillars, we propose a systems-level roadmap for developing climate-resilient rice cultivars capable of maintaining yield stability across a volatile combinatorial stress landscape. This synthesis provides a framework for translating mechanistic hormonal insights into field-applicable cultivars to ensure global food security.

CRISPR↗
PubMed1997

Dramatic increase of the RNA editing for glutamate receptor subunits during terminal differentiation of clonal human neurons.

RNA editing plays an important role in determining physiological characteristics of certain glutamate-gated receptor (GluR) channels such as Ca2+ permeability and desensitization kinetics. In one case, the editing changes a gene-encoded glutamine (Q) to an arginine (R) codon located in the channel-forming domain of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit GluR-B and also the kainate receptor subunits GluR5 and GluR6. Another case of RNA editing alters an arginine (R) to a glycine (G) codon at a position termed the "R/G" site of AMPA subunits GluR-B, C, and D. Double-stranded RNA-specific adenosine deaminases (DRADA) have been implicated as agents involved in the editing. By using a human teratocarcinoma cell line, NT2, we investigated the change of the RNA editing of GluR subunits in conjunction with the expression of two DRADA members, DRADA1 and DRADA2 genes, during neuronal differentiation. Whereas Q/R and R/G site RNA editing both become progressively activated in differentiating NT2 cells, the expression of the two DRADA genes can already be detected even in the undifferentiated NT2 cells. Development of the editing machinery appears to require, in addition to DRADA enzymes, a currently unidentified mechanism(s) that may become activated during neuronal differentiation.

Adenosine Deaminase↗
PubMed2003

Is the Trypanosoma brucei REL1 RNA ligase specific for U-deletion RNA editing, and is the REL2 RNA ligase specific for U-insertion editing?

It was shown previously that the REL1 mitochondrial RNA ligase in Trypanosoma brucei was a vital gene and disruption affected RNA editing in vivo, whereas the REL2 RNA ligase gene could be down-regulated with no effect on cell growth or on RNA editing. We performed down-regulation of REL1 in procyclic T. brucei (midgut insect forms) by RNA interference and found a 40-50% inhibition of Cyb editing, which has only U-insertions, as well as a similar inhibition of ND7 editing, which has both U-insertions and U-deletions. In addition, both U-insertion and U-deletion in vitro pre-cleaved editing were inhibited to similar extents. We also found little if any effect of REL1 down-regulation on the sedimentation coefficient or abundance of the RNA ligase-containing L-complex (Aphasizhev, R., Aphasizheva, I., Nelson, R. E., Gao, G., Simpson, A. M., Kang, X., Falick, A. M., Sbicego, S., and Simpson, L. (2003) EMBO J. 22, 913-924), suggesting that the inhibition of both insertion and deletion editing was not due to a disruption of the L-complex. Together with the evidence that down-regulation of REL2 has no effect on cell growth or on RNA editing in vivo or in vitro, these data suggest that the REL1 RNA ligase may be active in vivo in both U-insertion and U-deletion editing. The in vivo biological role of REL2 remains obscure.

Animals↗
PubMed1996

Hepatic gene transfer of the catalytic subunit of the apolipoprotein B mRNA editing enzyme results in a reduction of plasma LDL levels in normal and watanabe heritable hyperlipidemic rabbits.

Apolipoprotein (apo) B exists in two forms, the full length protein apoB-100 and the carboxyterminal-truncated apoB-48 that is synthesized in the intestine due to editing of the apoB mRNA which generates a premature stop codon. To determine whether gene transfer of the catalytic subunit of the apoB mRNA editing enzyme APOBEC-1 (apoB mRNA editing enzyme catalytic polypeptide 1) into the liver of rabbits reconstitutes hepatic apoB mRNA editing and how this affects the plasma levels of apoB-containing lipoproteins, we constructed an APOBEC-1 recombinant adenovirus (Ad APOBEC-1). After injection of Ad APOBEC-1 into normal New Zealand White (NZW) or Watanabe heritable hyperlipidemic (WHHL) rabbits, up to 50% of the hepatic apoB mRNA was edited and freshly isolated hepatocytes secreted predominantly apoB-48-containing lipoproteins. VLDL isolated from Ad APOBEC-1-treated NZW and WHHL rabbits contained both apoB-100 and apoB-48, whereas that from control rabbits infected with a beta-galactosidase recombinant adenovirus (Ad LacZ) contained exclusively apoB-100. VLDL from WHHL rabbits treated with Ad APOBEC-1 had the same particle size, lipid composition, and content of apolipoprotein E as VLDL from Ad LacZ-infected control animals. An increase of VLDL was observed in NZW and WHHL rabbits after infection with Ad APOBEC-1 as well as Ad LacZ. After injection of Ad APOBEC-1, LDL became undetectable in the plasma of NZW rabbits and was reduced by an average of 65% in the plasma of WHHL rabbits compared to Ad LacZ-infected controls. LDL from Ad APOBEC-1-infected WHHL rabbits contained only apoB-100. VLDL isolated from Ad APOBEC-1-infected WHHL rabbits were rapidly cleared from the circulation after injection into NZW rabbits. These results provide further evidence that the switch in the hepatic synthesis from exclusively apoB-100 to partly apoB-48 can result in a reduction of LDL formation that requires the full-length apoB-100.

APOBEC-1 Deaminase↗
PubMed2006

ChloroplastDB: the Chloroplast Genome Database.

The Chloroplast Genome Database (ChloroplastDB) is an interactive, web-based database for fully sequenced plastid genomes, containing genomic, protein, DNA and RNA sequences, gene locations, RNA-editing sites, putative protein families and alignments (http://chloroplast.cbio.psu.edu/). With recent technical advances, the rate of generating new organelle genomes has increased dramatically. However, the established ontology for chloroplast genes and gene features has not been uniformly applied to all chloroplast genomes available in the sequence databases. For example, annotations for some published genome sequences have not evolved with gene naming conventions. ChloroplastDB provides unified annotations, gene name search, BLAST and download functions for chloroplast encoded genes and genomic sequences. A user can retrieve all orthologous sequences with one search regardless of gene names in GenBank. This feature alone greatly facilitates comparative research on sequence evolution including changes in gene content, codon usage, gene structure and post-transcriptional modifications such as RNA editing. Orthologous protein sets are classified by TribeMCL and each set is assigned a standard gene name. Over the next few years, as the number of sequenced chloroplast genomes increases rapidly, the tools available in ChloroplastDB will allow researchers to easily identify and compile target data for comparative analysis of chloroplast genes and genomes.

Chloroplasts↗
PubMed2024

Induced proximity labeling and editing for epigenetic research.

Epigenetic regulation plays a pivotal role in various biological and disease processes. Two key lines of investigation have been pursued that aim to unravel endogenous epigenetic events at particular genes (probing) and artificially manipulate the epigenetic landscape (editing). The concept of induced proximity has inspired the development of powerful tools for epigenetic research. Induced proximity strategies involve bringing molecular effectors into spatial proximity with specific genomic regions to achieve the probing or manipulation of local epigenetic environments with increased proximity. In this review, we detail the development of induced proximity methods and applications in shedding light on the intricacies of epigenetic regulation.

Epigenesis, Genetic↗
PubMed2005

Simultaneous expression of apolipoprotein B mRNA editing enzyme and scavenger receptor BI mediated by a therapeutic gene expression system.

Cardiovascular diseases are often accompanied by elevated LDL particles and endothelial dysfunction. We have examined the possibility of concurrently reducing LDL levels and modulating endothelial function using a single helper-dependent adenovirus vector system to simultaneously express the apolipoprotein B mRNA editing enzyme (Apobec1) and the scavenger receptor, class B, type I (SR-BI) genes under the control of separate promoters (designated HD-C2). Apobec1 edits apoB mRNA at nucleotide C-6666 to produce truncated apoB48 and is normally expressed in small intestine only. SR-BI is a receptor for multiple ligands with distinct tissue-specific functions. Expression of Apobec1 in HepG2 cells resulted in apoB mRNA editing, leading to decreased apoB100 abundance (to 6% of control) and the appearance of apoB48. Editing of apoB mRNA in HepG2 cells resulted in decline in apoB mRNA levels of 50%. This was probably the result of nonsense-mediated decay of edited message, since over-expression of Apobec1 increased neither Apobec1 complementary factor (ACF) mRNA nor protein abundance. Over-expression of SR-BI in human endothelial cells activated endothelial nitric oxide synthase (eNOS) activity by phosphorylation of eNOS at residue Ser-1177 in the presence of HDL, leading to increased production of the anti-atherogenic molecule nitric oxide (NO). Taken together, this study demonstrates that using one vector delivery system to express two genes in two different cell types results in the cell-specific beneficial effects of decreasing apoB100 production and increasing eNOS activities. This combined gene expression approach may provide an improved therapeutic strategy by targeting multiple sites in the mechanism of cardiovascular injury.

APOBEC-1 Deaminase↗
PubMed1991

The cytochrome oxidase II gene in mitochondria of the sugar-beet Beta vulgaris L.

We have cloned and analyzed the sugar-beet mitochondrial gene for cytochrome oxidase subunit II (coxII). The sugar-beet and its deduced amino acid sequence were compared to its homologous coxII gene sequences from both monocot and dicot plants. It was found to be highly conserved (89-95%) compared to homologue in other plant species. The 780 bp coding sequence of the sugar beet coxII gene is interrupted at position 383 by a 1463 bp intron. This intron contains an additional 107 bp sequence that is not found in any of the plant coxII genes studied thus far. The structure of the intron suggests that a large intron existed in an ancestral coxII gene before monocots and dicots diverged in evolution. Three CGG codons in the sugar-beet coxII coding sequence align with conserved tryptophan residues in the homologous gene of other species, suggesting that RNA editing takes place also in sugar-beet mitochondria. In 13 out of 24 codons of coxII mRNA that were found to be edited in four other plants, the sugar-beet gene already utilizes the edited codons. This phenomenon may indicate that the mitochondrial genome in sugar-beet is phylogenetically more archaic relative to these plants. An additional sequence of 279 bp that is identical to the first exon of coxII was identified in the mtDNA of the sugar-beet. This 'pseudo-gene' is transcribed and its existence in the mitochondrial genome is unexplained.

Amino Acid Sequence↗
PubMed1992

The mitochondrial gene encoding ribosomal protein S12 has been translocated to the nuclear genome in Oenothera.

The Oenothera mitochondrial genome contains only a gene fragment for ribosomal protein S12 (rps12), while other plants encode a functional gene in the mitochondrion. The complete Oenothera rps12 gene is located in the nucleus. The transit sequence necessary to target this protein to the mitochondrion is encoded by a 5'-extension of the open reading frame. Comparison of the amino acid sequence encoded by the nuclear gene with the polypeptides encoded by edited mitochondrial cDNA and genomic sequences of other plants suggests that gene transfer between mitochondrion and nucleus started from edited mitochondrial RNA molecules. Mechanisms and requirements of gene transfer and activation are discussed.

Amino Acid Sequence↗