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 919 records · Page 51Linked to original sources
PubMed1997

The genomic organization of guide RNA genes in kinetoplastid protozoa: several conundrums and their solutions.

The guide RNA (gRNA) paradigm states that the uridine (U) insertion/deletion type of RNA editing is mediated by short 3' uridylylated gRNAs that are complementary to specific blocks of mature edited sequence. These gRNAs contain the edited sequence information in the form of guiding purine residues that can base pair with the inserted U's and do not base pair with encoded U's that are to be deleted. The minicircle gRNA genes in trypanosomatids are localized at specific sites within the variable region, with the number and the precise localization of genes also being species-specific. The total number of minicircle sequence classes and thereby minicircle-encoded gRNAs varies greatly between species and even between different strains of the same species, with the greatest number being in the trypanosome species. Several conundrums which appeared to raise problems for the gRNA paradigm arose during comparative analysis of minicircle gRNA gene organization. The solution of these conundrums has led to a better understanding of the function and evolution of this RNA modification phenomenon.

Animals↗
PubMed1994

RNA editing of the glutamate receptor subunits GluR2 and GluR6 in human brain tissue.

Editing of mRNA in the coding region of the second transmembrane domain of glutamate receptor subunits GluR2, GluR5, and GluR6 involves a change of the base A in genomic DNA to the base G in mRNA as described in rat brain. To determine whether this reaction occurs in humans as well as rats, we studied RNA editing of GluR2 and GluR6 in human brain. We compared the extent of editing in controls and cases with Huntington's disease. To assay the extent of editing in brain RNA, first strand cDNA was amplified using the polymerase chain reaction yielding a product across the region of the second transmembrane spanning segment in which editing takes place in rats. The PCR product was incubated with the restriction enzyme BbvI, which recognizes the sequence GCAGC present in the nonedited sequence of the mRNA in subunits GluR2 and GluR6. Thus, BbvI cuts the nonedited version but leaves the edited version intact. As in the rat, the GluR2 subunit mRNA was completely edited in human brain. The GluR6 subunit was nearly completely edited in all gray matter structures investigated including cortex, striatum, thalamus, hippocampus, amygdala, and cerebellum with extent of editing ranging from 89% in the cerebellum to 95% in the cortex and striatum. No significant differences in the extent of RNA editing were apparent in control versus Huntington's disease brains. To compare the extent of editing in neurons and glia in the brain, editing in cerebral cortex (predominantly gray matter and thus neurons) was compared with editing in corpus callosum (white matter and thus nearly completely glial cells).(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

Are 5S ribosomal RNA primary transcripts edited?

Comparative analysis of the nucleotide sequences of plant 5S rRNA genes shows numerous discrepancies with the mature 5S rRNAs. Detailed inspection of these differences revealed that they are mainly due to single nucleotide substitutions, insertions and deletions. In several cases also longer insertions were found, two of which are particularly interesting. Their location in loops resembles tRNA introns. One of these insertions is 79 nucleotides long and can potentially form a tRNA-like structure, with 50% homology to plant tRNAGly. This observation led us to propose that, in the maturation of some 5S rDNA transcripts, editing and splicing mechanisms may be involved.

Base Sequence↗
PubMed2005

[An estimation chart for the possibility of aspiration in patients with severe motor and intellectual disabilities: its reliability and accuracy].

Although the most common cause of death in patients with severe motor and intellectual disabilities (SMID) is aspiration pneumonia, there are no criteria to detect aspiration. We have been making an evaluation tool to detect aspiration in patients with SMID easily, in cooperation with the project of comprehensive study of disability, social health, and welfare, supported by the Ministry of Health, Labor and Welfare, Japan. Here we studied the reliability and accuracy of the 2001 edition of the "questionnaires for functions of eating and swallowing" and "estimation chart for the possibility of aspiration" in 20 patients with risk of aspiration (13 with cerebral palsy, six with acquired cerebral palsy and one with muscle disease). Family members or nursing staffs taking care of them answered the questionnaires. A pediatrician and an occupational therapist or speech therapist checked the chart. Reliability was checked by the agreement between the estimation of the two professionals, and accuracy was determined by comparing the results of the chart and videofluolography. The results showed good reliability (kappa 0.63) and accuracy (kappa 0.47). Based on these results and additional analysis of the check items, the new edition of the chart was established.

Cerebral Palsy↗
PubMed1996

Paramyxovirus RNA editing and the requirement for hexamer genome length.

Paramyxoviruses cotranscriptionally edit their P gene mRNA by the programmed insertion of G residues into a short G run contained within a larger purine run, via pseudo-templated transcription. The templates for paramyxovirus transcription are genome nucleocapsids in which each nucleoprotein subunit is associated with 6 nt, and only genomes whose lengths are multiples of 6 are found naturally or are replicated efficiently in transfected cell systems. We have examined the effect of varying total genome length on the frequency and number of insertions into the mRNA editing site in a transfected cell system, using constructs that generate mini-genome analogues. We found that, as long as the purine run sequence and the region immediately upstream were unaltered, editing occurred during mRNA synthesis independent of the precise length of the minigenome. However, when mini-genome constructs whose lengths were not multiples of 6 were used, insertions (or deletions) occurred during antigenome synthesis within the purine run, which strikingly restored the hexamer length. Genome length correction due to changes in the antigenome purine run length occurred only when the mini-genome was not a multiple of 6, and these changes were only poorly affected by mutations in the mRNA editing site and the region immediately upstream. Our results suggest that the mRNA editing site is a natural hotspot for viral polymerase slippage during genome replication, and that this site serves the dual and complementary function of maintaining hexamer genome length. The unusual requirement of paramyxoviruses for genomes of precise hexamer length may have evolved to maintain genome stability against insertions in the mRNA editing site during replication.

Base Composition↗
PubMed1993

RNA editing of apocytochrome b (cob) transcripts in mitochondria from two genera of plants.

Editing of the complete coding region of cob transcripts from two genera of plants has been studied by cDNA sequence analysis. Eighteen and nine C residues are edited into U in the mitochondrial transcripts from wheat and potato respectively. Both systems share eight common editing sites; ten codons edited in wheat are "pre-edited" at the genomic level in potato, and one codon edited in potato is "pre-edited" in wheat. Most amino-acid modifications lead to hydrophobic residues and increase the homology between the COB polypeptides and the corresponding protein of other species. In two out of the nine potato cDNA clones, an additional C-to-T modification, which also leads to a change in the encoded amino acid, was identified. Heterogeneity observed at the carboxy-terminus of the COB open reading frame in Triticum aestivum and Triticum timopheevi is not corrected by editing.

Apoproteins↗
PubMed2002

Effects of cocaine and reserpine administration on RNA editing of rat 5-HT2C receptor estimated by primer extension combined with denaturing high-performance liquid chromatography.

Serotonin 2C receptor (5-HT(2C)R) transcripts undergo RNA editing, generating pharmacologically different isoforms. To test whether the RNA editing of 5-HT(2C)R is regulated by serotonergic activity, effects of cocaine or reserpine administration in the rat cerebral cortex were examined. Although these drugs have been known to alter serotonin metabolism, no alterations in the RNA editing were found by the sequencing analysis. Towards high throughput analysis, we developed a non-RI method that allows accurate and rapid estimation of RNA editing by combining the primer extension with denaturing high-performance liquid chromatography (DHPLC). By using this, RNA editing efficiencies of 5-HT(2C)R in the midbrain and hippocampus as well as the cerebral cortex were examined, and no alterations were found among these regions. Our method using DHPLC is applicable to examine association of RNA editing with various diseases.

Amino Acid Sequence↗
PubMed2001

A single alteration 20 nt 5' to an editing target inhibits chloroplast RNA editing in vivo.

Transcripts of typical dicot plant plastid genes undergo C-->U RNA editing at approximately 30 locations, but there is no consensus sequence surrounding the C targets of editing. The cis-acting elements required for editing of the C located at tobacco rpoB editing site II were investigated by introducing translatable chimeric minigenes containing sequence -20 to +6 surrounding the C target of editing. When the -20 to +6 sequence specified by the homologous region present in the black pine chloroplast genome was incorporated, virtually no editing of the transcripts occurred in transgenic tobacco plastids. Nucleotides that differ between the black pine and tobacco sequence were tested for their role in C-->U editing by designing chimeric genes containing one or more of these divergent nucleotides. Surprisingly, the divergent nucleotide that had the strongest negative effect on editing of the minigene transcript was located -20 nt 5' to the C target of editing. Expression of transgene transcripts carrying the 27 nt sequence did not affect the editing extent of the endogenous rpoB transcripts, even though the chimeric transcripts were much more abundant than those of the endogenous gene. In plants carrying a 93 nt rpoB editing site sequence, transgene transcripts accumulated to a level three times greater than transgene transcripts in the plants carrying the 27 nt rpoB editing sites and resulted in editing of the endogenous transcripts from 100 to 50%. Both a lower affinity of the 27 nt site for a trans-acting factor and lower abundance of the transcript could explain why expression of minigene transcripts containing the 27 nt sequence did not affect endogenous editing.

Base Sequence↗
PubMed2004

Morphine use for at-home cancer patients in Japan.

Recently, many cancer patients have been cared for at home in Japan. Cancer pain control is one of the most important factors for terminal cancer patients to maintain functional lives at home. Morphine has long been the gold standard in the control of cancer pain. This paper examined the present status of the frequency of morphine use and its prescribing route for pain control in cancer patients at home monitored by doctors offering home care medicine in Japan. We reviewed the data based on the replies to questionnaires about morphine use in a textbook edited in 2001 by the doctors supportive of home care medicine nationwide in Japan. 301 (92.9%) among 324 doctors administered morphine for at-home cancer patients. 257 doctors' replies were analyzed as to the prescribed pattern of morphine after excluding data without information on the administration route. The oral administration was most frequently used in 247 (96.1%) doctors and rectal administration was used in 217 (84.4%) doctors, while intravenous injection and epidural infusions were less common. The pattern of morphine administration was similar between doctors who worked at hospitals and clinics, except that doctors who worked at hospitals administered subcutaneously more frequently than doctors who worked at clinics (69.2% in the hospital vs. 39.4% in the clinic setting). This study has revealed that morphine is commonly prescribed to control pain in at-home cancer patients by doctors who support home care medicine in Japan. The restricted administration routes of morphine among the doctors and less prevalent use of the subcutaneous routes in doctors who work at clinics are also shown in the home cancer care setting. These findings might result from mutual relationship between the thought and experience of doctors and clinical characteristics of patients under home care medicine.

Adult↗
PubMed1995

RNA editing of a group II intron in Oenothera as a prerequisite for splicing.

The trans-splicing group II intron c/d in the Oenothera mitochondrial nad1 gene is modified by RNA editing in domain 6. This C-to-U conversion generates the typical domain 6 structure, which prompted us to speculate that this RNA editing event might be essential for splicing. To test this hypothesis, we investigated the influence of unedited and edited sequences of the Oenothera intron on splicing in vitro. The stem of domain 6 of intron nad1-c/d was transplanted into the autocatalytic yeast intron aI5c, yielding chimeras with the genomic C and the edited U, respectively, 5' of the branchpoint A. When incubated under self-splicing conditions, only the edited chimera was released as a lariat, while the precursor with the genomically coded C remained inactive. Our results support the hypothesis that Oenothera group II intron nad1-c/d cannot be spliced from the primary transcript without previous editing in domain 6.

Base Sequence↗
PubMed1993

RNA editing in Newcastle disease virus.

The co-transcriptional editing of the Newcastle disease virus (NDV) P gene has been studied by sequence analysis of cloned viral genomic RNA and mRNA. Evidence has been obtained for the specific insertion of non-templated G nucleotides, the consequence of which is the generation of three populations of P gene-derived mRNAs. The three populations encode proteins (P, V and W) which have a common N-terminal region, but which utilize three different reading frames at their C termini. Paradoxically, NDV edits its P gene mRNA by the insertion of non-templated G residues in a manner similar to Sendai and measles viruses (P-->V editing) despite its apparent closer evolutionary relationship to the simian virus type 5, mumps and related group of viruses which edit a V genomic sequence to generate an mRNA to encode a functional P protein (V-->P editing).

Amino Acid Sequence↗
PubMed1997

Insertional editing in isolated Physarum mitochondria is linked to RNA synthesis.

The mitochondrial RNAs of Physarum polycephalum are edited efficiently by nucleotide insertion both in vivo and in isolated mitochondria. Our recent studies have demonstrated that nucleotide addition can occur within 14-22 nt of the 3' end of a nascent RNA, suggesting that insertional editing may be linked to transcription. To investigate the relationship between these processes, we have examined the effects of nucleotide concentration on templated and nontemplated nucleotide addition in isolated mitochondria. At very low CTP concentrations, transcription and editing proceed with high fidelity, but the efficiency of cytidine insertional editing decreases. Insertion of single uridine and dinucleotides is not diminished under conditions that yield unedited or partially edited C insertion sites, indicating that editing events occur independently of one another. Moreover, analysis of partially edited RNA demonstrates that single nucleotides can be added at dinucleotide insertion sites. Importantly, pulse-chase experiments indicate that nontemplated nucleotides are not inserted into previously synthesized RNA once editing conditions are restored, although RNA downstream of the unedited region is edited efficiently. This result indicates that insertional editing cannot occur posttranscriptionally under these conditions, and suggests that there is only a small "window of opportunity" in which nucleotide insertion can occur. Our data are consistent with an editing activity that functions in a strictly 5' to 3' direction and adds nucleotides at, or close to, the 3' end of nascent RNA in association with the transcription complex. Several possible models for the mechanism of insertional editing in Physarum are discussed.

Animals↗
PubMed1993

Group II intron RNA catalysis of progressive nucleotide insertion: a model for RNA editing.

The self-splicing bl1 intron lariat from mitochondria of Saccharomyces cerevisiae catalyzed the insertion of nucleotidyl monomers derived from the 3' end of a donor RNA into an acceptor RNA in a 3' to 5' direction in vitro. In this catalyzed reaction, the site specificity provided by intermolecular base pair interactions, the formation of chimeric intermediates, the polarity of the nucleotidyl insertion, and its reversibility all resemble such properties in previously proposed models of RNA editing in kinetoplastid mitochondria. These results suggest that RNA editing occurs by way of a concerted, two-step transesterification mechanism and that RNA splicing and RNA editing might be prebiotically related mechanisms; possibly, both evolved from a primordial demand for self-replication.

Adenosine↗
PubMed1983

The influence of editing on the performance of a computer program for serial comparison of electrocardiograms.

In this study, three tests of computer ECG analysis function were conducted: 1) interpretation of serial tracings using the single record analysis program, i.e. without serial comparisons; 2) interpretation of the same tracings using a computer-comparison program; and 3) interpretation of these tracings using not only a computer-comparison program but also an editing program which allows amending of each serial record and insertion of any corrections into the computer data base before the next comparison. There was an over-all reduction of 84% in the number of statement changes needed to produce a correct final report by using the combined comparison and editing program. When this combined program was used, 81% of all computer interpretations required no alteration, --a considerable saving of time in analyzing serial electrocardiographic tracings. Serial comparison was required in in 27--45% of all ECG's taken in four medical centers.

Arrhythmias, Cardiac↗
PubMed2007

Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society.

OBJECTIVE: Low birth weight remains a major cause of morbidity and mortality in early infancy and childhood. It is associated with an increased risk of health problems later in life, particularly coronary heart disease and stroke. A meeting was convened to identify the key health issues facing a child born small for gestational age (SGA) and to propose management strategies. PARTICIPANTS: There were 42 participants chosen for their expertise in obstetrics, peri- and neonatal medicine, pediatrics, pediatric and adult endocrinology, epidemiology, and pharmacology. EVIDENCE: Written materials were exchanged, reviewed, revised, and then made available to all. This formed the basis for discussions at the meeting. Where published data were not available or adequate, discussion was based on expert clinical opinions. CONSENSUS PROCESS: Each set of questions was considered by all and then discussed in plenary sessions with consensus and unresolved issues identified. The consensus statement was prepared in plenary sessions and then edited by the group chairs and shared with all participants. CONCLUSIONS: The diagnosis of SGA should be based on accurate anthropometry at birth including weight, length, and head circumference. We recommend early surveillance in a growth clinic for those without catch-up. Early neurodevelopment evaluation and interventions are warranted in at-risk children. Endocrine and metabolic disturbances in the SGA child are recognized but infrequent. For the 10% who lack catch-up, GH treatment can increase linear growth. Early intervention with GH for those with severe growth retardation (height sd score, <-2.5; age, 2-4 yr) should be considered at a dose of 35-70 microg/kg x d. Long-term surveillance of treated patients is essential. The associations at a population level between low birth weight, including SGA, and coronary heart disease and stroke in later life are recognized, but there is inadequate evidence to recommend routine health surveillance of all adults born SGA outside of normal clinical practice.

Adult↗