Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “operational RNA code”

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 19 recordsLinked to original sources
PubMed2026

The proteomic origin of the genetic code.

INTRODUCTION: The origin and evolution of the genetic code is a central problem in molecular biology. Classical models have emphasized stereochemistry, frozen accidents, or adaptive optimization, often treating proteins as passive products of preexisting codes. More recent views instead portray the code as a dynamic, coevolving system shaped by reciprocal interactions among amino acids, RNA, and early catalysts. AREAS COVERED: Here, I review efforts of phylogeny reconstruction of the history of tRNA, protein structural domains, and dipeptide sequences in proteomes. These complementary approaches allow exploration of the entry of amino acids and codons into the code, and the transition from an operational RNA code in the tRNA acceptor arm to the canonical code in the anticodon loop. Evidence for ancestral synthetase enzymes with dual functions in aminoacylation and peptide-bond formation, as well as early bidirectional (sense-antisense) coding reflected in dipeptide-antidipeptide emergence is also discussed. EXPERT OPINION: The genetic code is best viewed as a proteome-driven, evolvable system in which early peptides actively shaped coding rules by stabilizing structure, expanding chemical diversity, and enhancing catalysis. This perspective connects origin-of-life studies with modern efforts of code expansion, translational engineering, and peptide-based therapeutics, highlighting the impact of the code's proteomic origin.

Genetic Code↗
PubMed1990

New approaches to increase the expression and stability of cloned foreign genes in Escherichia coli.

A family of expression plasmid vectors were constructed by fusing the strong P2 promoter of the rrnB gene of Escherichia coli (coding for ribosomal RNA) to the lac operator, thereby eliminating regulatory sequences from the rrnB gene and placing the expression under lac repressor control. This promoter proved to be stronger in vivo than the well-known consensus tac promoter, and its strength could be further increased by converting the sequence to consensus. The stability of the recombinant proteins could be increased by fusion to various lengths of the N-terminal end of beta-galactosidase, or by inserting a synthetic oligonucleotide, coding for heptathreonine. A new method was developed for the stabilization of recombinant plasmids without antibiotic selection, based on the presence of an essential gene on the plasmid and its absence from the chromosome. The application of this method is illustrated by the example of a plasmid expressing human proinsulin.

Biotechnology↗
PubMed1986

RNA structural elements for expression in Escherichia coli. Alpha 1-antitrypsin synthesis using translation control elements based on the cII ribosome-binding site of phage lambda.

Analysis of a series of lambda cII::alpha 1-antitrypsin (alpha 1AT) gene fusions of different sizes showed that increased alpha 1AT expression correlated with the stabilisation of a particular computer-predicted RNA secondary structure. Moreover, significant synthesis of unfused alpha 1AT was achieved by reconstruction of this conformation to permit interaction between the upstream region of the ribosome-binding site and the first part of the alpha 1AT coding sequence. This high-level expression was dependent upon certain silent point mutations in the coding sequence, indicating that RNA primary and secondary structure determinants can operate in concert to dictate the efficiency of protein synthesis.

Bacteriophage lambda↗
PubMed1992

Adenine deaminase and adenine utilization in Saccharomyces cerevisiae.

Compared with other purine salvage and nitrogen catabolism enzymatic activities, adenine deaminase (adenine aminohydrolase [AAH]; EC 3.5.4.2) activity in Saccharomyces cerevisiae is uniquely regulated. AAH specific activity is not induced by adenine and is reduced sevenfold when cells are cultivated in medium containing proline in place of ammonium as the sole nitrogen source. Exogenous adenine enters metabolic pathways primarily via the function of either AAH or adenine phosphoribosyltransferase (APRT; EC 2.4.2.7). Exogenous adenosine cannot normally be utilized as a purine source. Strains efficiently utilized adenosine or inosine when grown in pH 4.5 medium containing Triton X-100. A recessive mutation permitting utilization of adenosine or inosine in standard media was isolated. In both situations, growth of purine auxotrophs required either AAH or APRT activity. With medium containing either ammonium or proline as a nitrogen source, minimum doubling times of purine auxotrophs deficient in either APRT or AAH were measured. In proline-based medium, AAH and APRT permitted equal utilization of exogenous adenine. In ammonium-based medium, the absence of APRT increased the minimum doubling time by 50%. Similar experiments using sufficient exogenous histidine to feedback inhibit histidine biosynthesis failed to affect the growth rates of adenine auxotrophs blocked in AAH or APRT, indicating that the histidine-biosynthetic pathway does not play a significant role in adenine utilization. The gene that encodes AAH in S. cerevisiae was isolated by complementation using yeast strain XD1-1, which is deficient in AAH, APRT, and purine synthesis. A 1.36-kb EcoRI-SphI fragment was demonstrated to contain the structural gene for AAH by expressing this DNA in Escherichia coli under control of the trp promoter-operator. Northern (RNA) studies using the AAH-, APRT-, and CDC3-coding regions indicated that AAH regulation was not mediated at the level of transcription or mRNA degradation.

Adenine↗
PubMed1991

[Cycle dependent expression of the gene coding for B2mRNA].

The relative contents of individual tissue specific RNA B2mRNAx was studied in the population of nuclear and poly(A)+ cytoplasmic RNA from the livers of intact, falsely operated and having suffered the partial liver resection rats. Dot-hybridization technique was used to study this transcript containing the transcribed copy of the B2 repetitive genetic element of rats. The expression of the gene coding for B2mRNAx takes place at the lower level in the liver induced to proliferation as compared with the one in the liver of intact animals. It is changed reproducibly in antiphase with the c-fos RNA and with major inclinations at the moments of cellular phases switch.

Animals↗
PubMed1976

Transitional control in Semliki forest virus infected cells.

The cistron of the 42 S RNA, which codes for other than structural proteins, is poorly translated in the middle of the growth cycle. The translational control operating in the infected cells is not expressed in cell-free protein synthesising systems programmed with the 42 S RNA, since mostly non-structural proteins are made in vitro. One of our temperature-sensitive mutants of SFV, ts-1, directs the synthesis of two non-structural proteins with molecular weights of 78,000 (ns-78) and 86,000 (ns-86) but only at the restrictive temperature. This indicates that the synthesis of the non-structural proteins is controlled by viral rather than cellular factor(s). Temperature shift experiments revealed that the control mechanism was only slowly affected by the change of the temperature.

Cell Line↗
PubMed1976

[Successes and prospects for genetic engineering].

The review of literature (1970-1976) on problems of gene engineering is given. Gene engineering is pointed out to be a new method of modern biology and a new page of modern molecular genetics. Gene engineering detected a real possibility of artificial creating living hybrid organisms, i.e. constructing functional recombinant DNA molecules according to a project of investigator, but not to possibilities of crossing. The determination of gene engineering (in contrast with genetical engineering) is given in the first division of the article. Genetical engineering is a construction of hybrid organisms on the basis of recombination between non-homologous chromosomes cy crossing. Genetical engineering is based on sex crossing, thus the application of this method is restricted by crossability (i.e. experiments in vivo), which possibilities are determined by taxonomical limits. Gene engineering is a new method of operating directly with genes. It permits constructing in vitro any hybrid genomes desirable. There is no limits of combining ability for gene engineering. Three main stages of constructing hybrid genomes should be taken into account for the proper determination of gene engineering as a method of genome constructing: 1) the gene isolation; 2) their cross-linking in vitro; 3) the transfer of hybrid DNA into recipient cell or its genome. The cardinal stage of gene engineering is the construction of hybrid DNA, cross-linking any initial DNAs from any remote animals, plants and bacteria. All the methods known of gene isolation are described. The chemical method of gene isolation is based on that case, when DNA of some gene differs in its physico-chemical characteristics from total DNA, for example, DNAs of genes coding ribosomal RNAs or sea urchine histone DNA. Isolation of promotors and operators using DNA dependent RNA polymerase, which recognizes promotors, repressor and operator DNA, should also be considered as the chemical method of gene isolation. Restrictase method, which is also well known, is convenuent because the restricts have long enough sticky ends, which is important for the following gene cross-linking. The method of total restriction, reported by Lederberg et al. and Debabov et al., is described. The phage method (in particular, Shimada method) is given, permitting the direct integration of lambda phage into a number of sites of Escherichia coli chromosome. Gene engineering method of gene isolation is mentioned, in particular, the data of Kameron et al. on hybrid phages carrying DNA ligase gene, and Clark a. Carbon on hybrid plasmids carrying triptophane and arabinose operons genes. These methods are called "shot gun". Methods of gene isolation from higher organisms are less developed. A method of gene isolation using so called colony hybridization (according to Grünstein and Hognes) is also given...

Bacteriophages↗
PubMed1992

Plastid origin of an extrachromosomal DNA molecule from Plasmodium, the causative agent of malaria.

Several species of Plasmodium have been shown to contain a circular extrachromosomal DNA molecule which is widely supposed to be mitochondrial DNA. However, it has recently been shown to have a number of features in common with chloroplast DNA. Here, a phylogenetic analysis of RNA polymerase coding sequences from the Plasmodium molecule has been carried out using distance matrix, maximum likelihood, parsimony and operator invariant methods. The analysis indicates that the molecule is in fact derived from an oxygenic photosynthetic organism and should be regarded as plastid DNA. This suggests that Plasmodium originated from a phototroph that has lost the capacity to photosynthesize.

Amino Acid Sequence↗
PubMed1988

Inhibition of cytochrome P-450p (P450IIIA1) gene expression during liver regeneration from two-thirds hepatectomy in the rat.

Regenerating liver from partial hepatectomy (HPX) is known to exhibit a strong and transient deficiency in both spectrally detectable microsomal cytochrome P-450 (P-450) and related monooxygenase activities. Male Wistar rats (250-300 g) were HPX or sham operated and liver was excised at different times after operation. The time course of accumulation of five different forms of P-450 (including P-450b/e, P-450c, P-450d, P-450p and P-450UT-A) was determined in the regenerating liver, by Western blots developed with specific antibodies. With the exception of P-450c, whose level was not affected, the accumulation of other forms strongly decreased during the first 24 hr after HPX. For P-450b/e and P-450d, 80% of initial level was restored at 96 hr, whereas for P-450p and P-450UT-A, two major forms in control rat liver, the accumulation was only 20-25% of the initial, 1 week after HPX. No significant decrease was observed in sham operated animals. Plasmid pDex 12 containing a cDNA insert coding for P-450p was used to further investigate the effects of HPX on P-450p mRNA level and gene transcription. Northern blot analysis of RNA from regenerating liver (cDNA insert of pDex 12 being used as a probe) demonstrated that P-450p mRNA level decreased strongly to a minimum 12 hr after operation. This was correlated with a strong and transient decrease in P-450p gene transcription determined from nuclear run on experiments, the time course of which, however, did not account for the early decrease in mRNA level. We conclude that P-450p deficiency in the regenerating liver results from a combination of transient inhibition of gene transcription and early increase of mRNA degradation. Time course and amplitude of the decrease in P-450 UT-A accumulation suggest an inhibition of gene transcription as observed with P-450p.

Animals↗
PubMed2026

Whole-transcriptome RNA sequencing and ceRNA network analyses provide novel insights into the antibacterial immune response of Hippocampus abdominalis against Vibrio harveyi.

Long non-coding RNAs (lncRNAs) stand as newly-arisen molecular types that exert regulatory effects, able to operate as competitive endogenous RNAs (ceRNAs) to engage microRNAs (miRNAs) in interaction, resulting in the recovery of target mRNA expression and activity. Increasing evidences indicate that the ceRNA network affects various biological processes in mammals, including development, cellular differentiation, metabolism, immune response, and disease pathogenesis. In teleost fish, the lncRNA-miRNA-mRNA regulatory networks have been reported occasionally. However, up to now, the roles of lncRNAs in the big-belly seahorse (Hippocampus abdominalis) remains unclear. In this study, we reported for the first time, via whole-transcriptome RNA sequencing, the lncRNA mediated ceRNA regulatory network in Vibrio harveyi-infected H. abdominalis. A total of 4197 differentially expressed mRNAs (DE-mRNAs), 1317 DE-lncRNAs, and 183 DE-miRNAs were identified. Furthermore, the crosstalk between miRNAs and lncRNAs as well as between miRNAs and mRNAs was inferred based on the negative correlations between miRNAs and their target lncRNAs/mRNAs. A core immune associated lncRNA-miRNA-mRNA putative regulatory network was thus constructed, comprising 211 lncRNA-miRNA and 224 mRNA-miRNA pairs. In conclusion, our findings provide an integrative overview of the ceRNA regulatory networks on the underlying immune responses to V. harveyi infection in the big-belly seahorse, and offer a solid theoretical foundation for the comparative immunological research of teleost fish.

Animals↗
PubMed2026

EGFR-co-amplified lncRNA ELDR drives glioblastoma tumorigenicity by enhancing BMI1 activity.

BACKGROUND: In glioblastoma (GBM), epidermal growth factor receptor (EGFR) amplification, one of the most prevalent genetic alterations, often occurs on extrachromosomal DNAs (ecDNAs) that contain amplified oncogenes and regulatory elements, driving tumor progression. Despite the central oncogenic role of EGFR amplification, therapeutic strategies targeting EGFR have demonstrated limited clinical efficacy, suggesting that additional mechanisms may underlie EGFR-driven GBM malignancy and treatment resistance. Long non-coding RNAs (lncRNAs) are critical regulators in cancer; however, the roles of EGFR-associated lncRNAs-particularly those localized on ecDNA-in GBM tumorigenicity and therapeutic resistance remain poorly understood. METHODS: Transcriptomic and genomic analyses were performed to identify lncRNAs co-amplified with EGFR. Biochemical and molecular biological studies were carried out to reveal the mechanisms. In vivo xenograft models were used to evaluate the tumorigenicity and the therapeutic efficacy of combination treatment strategies. RESULTS: The lncRNA EGFR long non-coding downstream RNA (ELDR) was co-amplified with EGFR on ecDNA and chromosomes and was associated with poor prognosis in glioma. ELDR promoted GBM tumorigenicity through a BMI1-dependent epigenetic mechanism operating in parallel with canonical EGFR signaling. Mechanistically, ELDR interacted with purine-rich element-binding protein A (PURA), disrupted the inhibitory PURA-BMI1 interaction, and thereby enhanced the activity of BMI1, a core component of Polycomb repressive complex 1 (PRC1). Therapeutically, combining a BMI1 inhibitor or ELDR-targeting antisense oligonucleotides (ASOs) with an EGFR inhibitor erlotinib significantly enhanced antitumor efficacy in preclinical models of  EGFR  -amplified GBM with high ELDR expression. CONCLUSION: EGFR co-amplified ELDR promotes GBM tumorigenicity by enhancing BMI1 activity. Targeting the ELDR-BMI1 axis in combination with EGFR inhibition represents a promising therapeutic strategy for a subset of  EGFR  -amplified GBMs with high ELDR expression.

EGFR↗
PubMed1989

Regulated expression of foreign genes in mammalian cells under the control of coliphage T3 RNA polymerase and lac repressor.

Systems that stringently regulate the expression of individual genes within a complex genetic background have contributed greatly to the analysis of gene function. In this report the development of a highly regulated expression system in mammalian cells is described in which transcription of a foreign gene is mediated by the bacteriophage T3 RNA polymerase under the control of the Escherichia coli lac repressor. Rabbit kidney cell lines have been established that constitutively express the phage RNA polymerase and lac repressor. The two bacterial proteins regulate the transcription of the coding sequence of the firefly luciferase, which has been placed under the control of a T3 promoter/lac operator fusion. In the presence of the inducer isopropyl beta-D-thiogalactoside, efficient T3 polymerase-dependent transcription is observed, which is tightly repressed in the absence of inducer. Translation of the T3 transcripts can be mediated by vaccinia virus functions. The demonstration that a specific transcription activity can be regulated over a range of several orders of magnitude in higher eukaryotic cells by using a highly specific and nontoxic inducer has broad implications for a variety of studies.

Animals↗
PubMed1975

Polarity in segments of the Escherichia coli trp operon with deleted intraoperonic translational initiation signals.

The effect of deletion of the operator-distal genes of the trp operon, including the trpE-trpD intercistronic punctuation point, on the degree of transcriptional polarity (in this case the effect of a nonsense mutation on the level of mRNA from the distal part of the very gene where the mutation is located) was investigated. Double mutants which contain a nonsense mutation and a deletion in trpE were constructed, and the degree of transcriptional polarity was estimated by the decrease in messenger RNA for the operator-distal trpE beyond the nonsense mutation, as well as by the production of truncated messenger RNA for the region of trpE proximal to the nonsense mutation. The content of mRNA of operator-distal trpE and the size of the mRNA of operator-proximal trpE of the double mutants show that transcriptional polarity is not relaxed as a function of distance of the nonsense mutation from the operator-distal end of the trpE segment (at which the subsequent high efficiency translational initiation signal has been deleted). These findings are consistent with the conclusion that the degree of polarity depends on the distance of the nonsense mutation from the subsequent translation initiation signal, but not on its distance from the operator-distal end, including possible translational or transcriptional termination signals.

Escherichia coli↗
PubMed1986

Mitomycin C-induced bidirectional transcription from the colicin E1 promoter region in plasmid ColE1.

Treatment of a colicinogenic culture with mitomycin C induces convergent transcription from two adjacent promoters at the beginning of the colicin E1 gene. S1-mapping and primer extension assays indicate that the mitomycin C-inducible transcripts correspond to colicin E1 mRNA (cea mRNA) and to a transcript, designated RNA-C, that may code for an entry exclusion function. Nucleotide sequences that strongly resemble a consensus sequence for LexA protein binding sites span the transcription start points for cea mRNA and RNA-C. These putative operator sequences overlap by one base pair and bind LexA protein (Ebina, Y., Takahara, Y., Kishi, F., Nakazawa, A. and Brent, R. (1983) J. Biol. Chem. 258, 13258-13261). The data suggest that mitomycin C-induced bidirectional transcription from the cea mRNA and RNA-C promoters is controlled by the SOS regulatory system of Escherichia coli.

Bacteriocin Plasmids↗
PubMed2024

Construction of an immunogenic cell death-related LncRNA signature to predict the prognosis of patients with lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common malignant diseases worldwide. This study aimed to construct an immunogenic cell death (ICD)-related long non-coding RNA (lncRNA) signature to effectively predict the prognosis of LUAD. METHODS: The RNA-sequencing and clinical data of LUAD were downloaded from The Cancer Genome Atlas (TCGA). Least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox proportional hazard regression analysis were utilized to construct lncRNA signature. Then, the reliability of the signature was evaluated in the training, validation and whole cohorts. The differences in the immune landscape and drug sensitivity between the low- and high-risk groups were analyzed. Finally, the expression level of the selected ICD-related lncRNAs in LUAD cell lines via reverse transcription quantitative PCR (RT-qPCR). CCK-8 and transwell assays were performed to study biological function of AC245014.3. RESULTS: A signature consisting of 5 ICD-related lncRNAs was constructed. Kaplan Meier (K-M) survival analysis showed shorter overall survival (OS) in high-risk group. The receiver operating characteristic (ROC) curves and Multivariate Cox regression analysis showed the signature was good predictive and independent prognostic factor in LUAD. Moreover, the high-risk group had a lower level of antitumor immunity and was less sensitive to some chemotherapeutics and targeted drugs. Finally, the expression level of selected ICD-related lncRNAs was validated in LUAD cell lines by RT-qPCR. Knockdown of AC245014.3 significantly suppressed LUAD proliferation, migration and invasion. CONCLUSIONS: In this study, an ICD-related lncRNA signature was constructed, which could accurately predict the prognosis of LUAD patients and guide clinical treatment.

Humans↗