Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Base editing”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources

Glutamate receptor RNA editing in vitro by enzymatic conversion of adenosine to inosine.

RNA encoding the B subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of ionotropic glutamate receptor (GluR-B) undergoes a posttranscriptional modification in which a genomically encoded adenosine is represented as a guanosine in the GluR-B complementary DNA. In vitro editing of GluR-B RNA transcripts with HeLa cell nuclear extracts was found to result from an activity that converts adenosine to inosine in regions of double-stranded RNA by enzymatic base modification. This activity is consistent with that of a double-stranded RNA-specific adenosine deaminase previously described in Xenopus oocytes and widely distributed in mammalian tissues.

Adenosine↗

RNA editing and alternative splicing generate mRNA transcript diversity from the Drosophila 4f-rnp locus.

Extensive sequencing of genomic 4f-rnp and 15 cDNA clones isolated from libraries of 0-4-h embryos, pupae, and adult heads from Drosophila melanogaster has enabled identification of factors resulting in transcript sequence diversity. The 4f-rnp gene contains eight small introns. Among non-edited cDNAs, one transcript class potentially encodes a 943-amino-acid protein, within which several motifs are predicted, including a single C-terminal RNA-binding domain. Intron 5 is retained in all cDNAs examined except for a pupal cDNA, where it is excised. This potentially introduces an in-frame stop codon and predicts a truncated protein of 639 amino acids. One adult head transcript class is edited, some 31% of As being converted to Gs exclusive of edits within introns. An edit site in intron 4 changes a canonical 3'-terminal AG to GG, which interferes with splicing and is predicted to introduce a stop codon. A potential editing substrate recognition element in 4f-rnp contains the weak consensus sequence: 5'-G-G-G-N-A-A-G-3', which may interact with double-stranded RNA adenosine deaminase following pairing of 4f-rnp mRNA with an antisense transcript. It is possible that extensive editing in 4f-rnp destabilizes transcripts and thus provides a novel mechanism for post-transcriptional control of gene expression, although resolution of this point will require study of additional edited transcripts.

Alternative Splicing↗

Incomplete editing of rps12 transcripts results in the synthesis of polymorphic polypeptides in plant mitochondria.

C-to-U editing causes specific nucleotide changes in plant mitochondrial nRNAs that are required for the restoration of the evolutionarily conserved amino acid sequence. Transcripts for the ribosomal protein S12 gene (rps12) have six C-to-U editing sites and are highly heterogeneous as a result of incomplete editing. immunological analysis demonstrated that unedited or partially edited transcripts as well as edited mRNAs are translated. The edited rps12 translation products accumulate as ribosomal subunits, but the unedited rps12 translation products are present as unassembled subunits and are not detected in the ribosomes. Thus, gene expression is polymorphic as a result of incomplete C-to-U editing, and aberrant polypeptides are present from the translation of these mRNAs. However, because only the edited translation products accumulate in mitochondrial ribosomes, the overall expression of rps12 is rendered coherent by the selection

Amino Acid Sequence↗

Structure and activities of group II introns.

Group II introns are found in eubacteria and eubacterial-derived, organellar genomes. They have ribozymic activities, by which they direct and catalyze the splicing of the exons flanking them. This chapter reviews the secondary structure and known tertiary interactions of the ribozymic component of group II introns in relation to the problems of specifying splice sites and building a catalytic core. We pay special attention to the relationship between the transesterification and hydrolytic modes of initiating splicing and the stereospecificities of these reactions. A number of group II introns encode proteins of the reverse transcriptase family; the activity of these proteins enables the host introns to change genomic locations by mechanisms that are only beginning to be deciphered. Finally, we briefly discuss multipartite and post-transcriptionally edited group II introns, together with the intron microcosm of Euglena gracilis chloroplasts and the possible relationships between group II and spliceosome-catalyzed splicing processes.

Animals↗

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.

The mle(napts) mutation causes temperature-dependent blockade of action potentials resulting from decreased abundance of para-encoded Na+ channels. Although maleless (mle) encodes a double-stranded RNA (dsRNA) helicase, exactly how mle(napts) affects para expression remained uncertain. Here, we show that para transcripts undergo adenosine-to-inosine (A-to-I) RNA editing via a mechanism that apparently requires dsRNA secondary structure formation encompassing the edited exon and the downstream intron. In an mle(napts) background, >80% of para transcripts are aberrant, owing to internal deletions that include the edited exon. We propose that the Mle helicase is required to resolve the dsRNA structure and that failure to do so in an mle(napts) background causes exon skipping because the normal splice donor is occluded. These results explain how mlen(napts) affects Na+ channel expression and provide new insights into the mechanism of RNA editing.

Action Potentials↗

Brazilian medical publications: citation patterns for Brazilian-edited and non-Brazilian literature.

Today, the quality of a scientific article depends on the periodical in which it is published and on the number of times the article is cited in the literature. In Brazil, the criteria for the evaluation of this scientific production are improving. However, there is still some resistance, with authors arguing that Brazilian publications must be preferentially addressed to the national readers and, therefore, they should ideally be written in Portuguese. In order to determine the kind of scientific journals cited in the reference lists of articles published in medical periodicals edited in Brazil, in the present study we determine the rate of Portuguese/English citations. Three issues of 43 periodicals (19 indexed in SciELO, 10 in PubMed, 10 in LILACS, and 4 in the ISI-Thompson base) of different medical specialties were analyzed, and the number of both Portuguese and English citations in the reference list of each article was recorded. The results showed that in Brazilian-edited journals the mean number of citations/article was 20.9 +/- 6.9 and the percentage of citations of international non-Brazilian periodicals was 86.0 +/- 11.2%. Of the latter, 94.4 +/- 7.0 are indexed by ISI-Thompson. Therefore, we conclude that Brazilian medical scientists cite the international non-Brazilian periodicals more than the national journals, and most of the cited papers are indexed by ISI-Thompson.

Bibliometrics↗

The psbL gene from bell pepper (Capsicum annuum): plastid RNA editing also occurs in non-photosynthetic chromoplasts.

We have determined the nucleotide sequence of the plastid psbL gene from bell pepper. This gene has an ACG as a first codon. Isolation of RNA from pepper leaves and ripe fruits and subsequent sequencing of the psbL cDNA revealed that this ACG codon is post-transcriptionally edited into an AUG initiation codon in both leaves and fruits. These data indicate that the RNA editing machinery which exists in chloroplasts is still functional in chromoplasts from ripe fruits.

Amino Acid Sequence↗

International Journal of Occupational Medicine and Environmental Health in world documentation services: the SCOPUS based analysis of citation.

A high classification of scientific journals in the ranking of international transfer of knowledge is reflected by other researchers' citations. The International Journal of Occupational Medicine and Environmental Health (IJOMEH) is an international professional quarterly focused on such areas as occupational medicine, toxicology and environmental health edited in Poland. IJOMEH, published in English, is indexed in numerous world information services (MEDLINE, EMBASE, EBSCO, SCOPUS). This paper presents the contribution of IJOMEH publications to the world circulation of scientific information based on the citation analysis. The analysis, grounded on the SCOPUS database, assessed the frequency of citations in the years 1996-2005. Journals in which they have been cited were retrieved and their list is also included.

Databases, Factual↗

RNA splicing in higher plant mitochondria: determination of functional elements in group II intron from a chimeric cox II gene in electroporated wheat mitochondria.

Higher plant mitochondria mainly contain group II introns presenting a secondary structure with six helical domains linked to a central hub. Experimental evidence of functional elements in higher plant mitochondria introns is limited since they are unable to undergo self-splicing and the definition of functional domains is based on data obtained from yeast autocatalytic introns. Here we study the role of putative functional elements required for the splicing reaction. The exon-binding and intron-binding sites (EBS and IBS, respectively), and the domain 6, which is involved in lariat formation, were analysed by site-directed mutagenesis and transient expression in electroporated mitochondria. The data presented here demonstrate the role of EBS1-IBS1 and EBS2-IBS2 interactions and reveal a new secondary-structure interaction. The role of the C to U editing conversion in the IBS1 motif is discussed.

Base Sequence↗

Mutational specificity of a proof-reading defective Escherichia coli dnaQ49 mutator.

The dnaQ (mutD) gene product which encodes the epsilon-subunit of the DNA polymerase III holoenzyme has a central role in controlling the fidelity of DNA replication because both mutD5 and dnaQ49 mutations severely decrease the 3'-5' exonucleolytic editing capacity. It is shown in this paper that more than 95% of all dnaQ49-induced base pair substitutions are transversions of the types G:C-T:A and A:T-T:A. Not only is this unusual mutational specificity precisely that observed recently for a number of potent carcinogens such as benzo(a) pyrene diolepoxide (BPDE) and aflatoxin B1 (AFB1), which are dependent on the SOS system to mutagenize bacteria, but it is also seen for the constitutively expressed SOS mutator activity in E. coli tif-1 strains as well as for the SOS mutator activity mediated gap filling of apurinic sites. Because the G:C-T:A and A:T-T:A transversions can either result from the insertion of an adenine across from apurinic sites or arise due to the incorporation of syn-adenine opposite a purine base, we postulate that the DNA polymerase III holoenzyme also has a reduced discrimination ability in a dnaQ49 background. The introduction of a lexA (Ind-) allele, which prevents the expression of SOS functions, led to a significant reduction in the dnaQ49-caused mutator effect. Both, the mutational specificity observed and the partial lexA+ dependence of the mutator effect provoke a reanalysis of the hypothesis that the DNA polymerase III holoenzyme can be converted into the postulated but until now unidentified SOS polymerase.

Anticodon↗

Simultaneous alpha/beta spin-state selection for (13)C and (15)N from a time-shared HSQC-IPAP experiment.

Two novel HSQC-IPAP approaches are proposed to achieve alpha/beta spin-state editing simultaneously for (13)C and (15)N in a single NMR experiment. The pulse schemes are based on a time-shared (TS) 2D (1)H,(13)C/(1)H,(15)N-HSQC correlation experiment that combines concatenated echo elements for simultaneous J(CH) and J(NH) coupling constants evolution, TS evolution of (13)C and (15)N chemical shifts in the indirect dimension and heteronuclear alpha/beta-spin-state selection by means of the IPAP principle. Heteronuclear alpha/beta-editing for all CH( n ) (n = 1-3) and NH( n ) (1-2) multiplicities can be achieved in the detected F2 dimension of a single TS-HSQC-F2-IPAP experiment. On the other hand, an alternative TS-HSQC-F1-IPAP experiment is also proposed to achieve alpha/beta-editing in the indirect F1 dimension. Experimental and simulated data is provided to evaluate these principles in terms of sensitivity and performance simultaneously on backbone and side-chain CH, CH(2), CH(3), NH, and NH(2) spin systems in uniformly (13)C/(15)N-labeled proteins and in small natural-abundance peptides.

Carbon Isotopes↗

The influence of acculturation on the Wisconsin Card Sorting Test by Mexican Americans.

This study examined the speculation that the Wisconsin Card Sorting Test (WCST) might be a relatively culture-free neuropsychological test. The relationship between level of acculturation and performance on the Spanish version of the WCST was investigated, using a sample of Mexican American adults (N=52). When the sample was divided into two groups based on level of acculturation as measured by the Acculturation Rating Scale for Mexican Americans--2nd Edition, within-group contrasts demonstrated that higher levels of acculturation significantly improved performance on the WCST. The performance of this sample was compared to select Spanish norms, finding no clinically significant differences. Contrasts with English norms for the WCST yielded significant differences on a majority of the WCST measures, demonstrating that the English norms are inappropriate for use with this population. This study concludes that the WCST is not a culture-free neuropsychological test.

Acculturation↗

Towards a CRISPeR understanding of homologous recombination with high-throughput functional genomics.

CRISPR-dependent genome editing enables the study of genes and mutations on a large scale. Here we review CRISPR-based functional genomics technologies that generate gene knockouts and single nucleotide variants (SNVs) and discuss how their use has provided new important insights into the function of homologous recombination (HR) genes. In particular, we highlight discoveries from CRISPR screens that have contributed to define the response to PARP inhibition in cells deficient for the HR genes BRCA1 and BRCA2, uncover genes whose loss causes synthetic lethality in combination with BRCA1/2 deficiency, and characterize the function of BRCA1/2 SNVs of uncertain clinical significance. Further use of these approaches, combined with next-generation CRISPR-based technologies, will aid to dissect the genetic network of the HR pathway, define the impact of HR mutations on cancer etiology and treatment, and develop novel targeted therapies for HR-deficient tumors.

Gene Regulatory Networks↗