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Results for “operational RNA code”

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At least 199 records · Page 11Linked to original sources

PubMed1995

Triplet code-independent programming of living systems organisation by DNA: the link with intelligence and memory.

Previous suggestions from this laboratory (3), (a) that within its molecular electronic structure, DNA houses a computer-analog program of immense complexity, operating independently of, but complementary to, triplet coding and (b) that, inter alia, this program is the driving force for organising and executing the construction of species individuals in three dimensions, are extended in the present communication. It is now concluded that the DNA program also embodies an 'intelligence' component, which extends its organising ability both qualitatively and quantitatively beyond any of the heavily circumscribed 'self-organising' attributes claimed to be associated with naturally occurring inanimate systems. Further, that as part of the developmental process, a program component organises the fabrication of mammalian central nervous systems, including that of human beings with the associated attributes of intelligence, creativity and constructional skills. It is further suggested that the sophisticated random access memory system associated with human beings in particular may be explicable in terms of an extension of the DNA programming system: basically this involves the latter operating as computer-type 'hardware' for the storage of long-term memory and interacting with, primarily, glial cell RNA, acting as 'software' and storing short term traces. Finally, it is suggested that such an interrelationship between DNA/RNA molecular electronic structures can provide the necessary memory storage capacity and flexibility and also facilitates random access to the long-term DNA memory store.

Animals↗

PubMed1991

Point mutations upstream of the yeast ADH2 poly(A) site significantly reduce the efficiency of 3'-end formation.

The sequences directing formation of mRNA 3' ends in Saccharomyces cerevisiae are not well defined. This is in contrast to the situation in higher eukaryotes in which the sequence AAUAAA is known to be crucial to proper 3'-end formation. The AAUAAA hexanucleotide is found upstream of the poly(A) site in some but not all yeast genes. One of these is the gene coding for alcohol dehydrogenase, ADH2. Deletion or a double point mutation of the AAUAAA has only a small effect on the efficiency of the reaction, and in contrast to the mammalian system, it is most likely not operating as a major processing signal in the yeast cell. However, we isolated point mutations which reveal that a region located approximately 80 nucleotides upstream of the poly(A) site plays a critical role in either transcription termination, polyadenylation, or both. These mutations represent the first point mutations in yeasts which significantly reduce the efficiency of 3'-end formation.

Alcohol Dehydrogenase↗

PubMed1993

Interplay of the liver-enriched trans-acting factors, DBP and HNF1, in the transactivation of human IGFBP-1 promoter.

In the liver, expression of insulin-like growth factor binding protein-1 (IGFBP-1) is regulated essentially at the transcriptional level, at least in part by HNF1. In this study, the functional role of DBP and C/EBP (which have several potential binding sites on the IGFBP-1 proximal promoter) have been investigated. Transient co-transfection of the reporter plasmid, pBP-1341 and eukaryotic expression vectors which code for DBP and C/EBP in human cell lines Hep3B, HepG2 and C33 showed that IGFBP-1 promoter activity was unchanged by C/EBP, but increased between 2 and 7 times by DBP (depending on the cell line). In addition, DBP and HNF1 were capable of functional co-operation in activating the IGFBP-1 promoter. Our results support the notion of DBP being involved in limited tissue specificity of IGFBP-1 expression.

CCAAT-Enhancer-Binding Proteins↗

PubMed1995

Intragenic domains of strand-specific repair in Escherichia coli.

Heterogeneity of DNA repair has been observed at different levels of genomic organization, including chromatin domains, expressed genes and DNA strands. If heterogeneity also existed intragenically, it could reveal fine details of the excision repair mechanism in vivo. Here we measure the frequency of UV-induced cyclobutane pyrimidine dimers at individual nucleotides within defined portions of two Escherichia coli genes, lacl and lacZ, at various times after irradiation. Two domains of differential repair rates were apparent, with repair being slow at nucleotides adjacent to the transcription start sites. In lacZ, the domain of faster repair began 32 bases downstream of the transcription start site and required the mfd gene. Since mfd codes for a transcription-repair coupling factor, this transcription-coupled repair system evidently becomes operative downstream of the initiation complex region in vivo. Unexpectedly, however, (1) an mfd mutation reduced repair in the downstream domain even when transcription was at a very low level and (2) induction of lacZ transcription with isopropyl-beta-D-thiogalactoside overcame this reduction. Evidently, the Mfd transcription-repair coupling factor is required for basal levels of strand-specific repair in this gene, but induced levels of repair are related to transcription through another mechanism.

Bacterial Proteins↗

PubMed1990

Codon recognition mechanisms in plant chloroplasts.

In chloroplasts, all 61 sense codons are found in chloroplast (cp) DNA sequences coding for proteins. However among the sequenced cp tRNAs or tRNA genes, tRNAs with anticodons complementary to codons CUU/C (Leu), CCU/C (Pro), GCU/C (Ala) and CGC/A/G (Arg) [or CGC/A (Arg) in Marchantia] have not been found. In this paper we show that cp tRNA(Ala)(U*GC) cp tRNA(Pro)(U*GG) and cp tRNA(Arg)(ICG) are able to decode the corresponding four-codon family. In the case of leucine codons CUU/C, we show that 'U:U and U:C wobble' mechanisms can operate to allow the reading of these codons by cp tRNA(Leu)(UAm7G).

Amino Acid Sequence↗

PubMed2001

The lac operator-repressor system is functional in the mouse.

We report the successful transfer of a fully functional lac operator-repressor gene regulatory system to the mouse. The key component is a lac repressor transgene that resembles a typical mammalian gene both in codon usage and structure and expresses functional levels of repressor protein in the animal. We used the repressor to regulate the expression of a mammalian reporter gene consisting of the tyrosinase promoter embedded with three short lac operator sequences and the tyrosinase coding sequence. Pigmentation of the mouse was controlled by the interaction of the lac repressor with the regulatable Tyrosinase transgene in a manner that was fully reversible by the lactose analog IPTG. Direct control of mammalian promoters by the lac repressor provides tight, reversible regulation, predictable levels of de-repressed expression, and the promise of reversible control of the endogenous genome.

Animals↗

PubMed2026

Functional chimeric mRNAs encode proteins in mammalian immunity.

Individual mammalian mRNAs and proteins are typically believed to originate from single genomic loci, with isoform diversity arising through cis-splicing of pre-mRNA. Whether mRNA from distant genes can undergo trans-splicing to generate functionally relevant chimeric transcripts has remained unclear. Here we develop a pipeline combining long-read direct RNA sequencing with non-targeted and targeted validation to identify chimeric transcripts in macrophages. Chromatin conformation capture studies reveal that inflammation induces interchromosomal DNA interactions, positioning parent genes proximally to facilitate the formation of chimeric mRNA. Notably, we identify a protein-coding chimeric mRNA representing a fusion between the pore-forming protein gasdermin D (GSDMD)1,2 and a C-terminal domain translated out of frame from Tmem106a (Gsdmd-Tmem106a) in mice. We show that inflammasome priming upregulates Gsdmd-Tmem106a, with the protein localizing to the plasma membrane. After activation of the inflammasome, GSDMD-TMEM106A directly interacts with canonical GSDMD N termini to accelerate and enhance pore formation and IL-1β release. Finally, we show that GSDMD-TMEM106A balances host defence and immunopathology in vivo: its loss protects against lethal sepsis but compromises antibacterial defence, whereas overexpression enhances host protection while increasing sepsis lethality. We establish that protein-coding chimeric mRNAs formed by regulated transcript fusion events are operative during inflammation and immunity.

Journal Article↗

PubMed1991

Fibronectin and collagen gene expression in healing experimental colonic anastomoses.

The temporal and spatial expression of fibronectin and type I and III collagen genes were studied 1-14 days after surgery in the healing rat colonic anastomosis using recombinant deoxyribonucleic acid techniques. Messenger ribonucleic acids (mRNAs) coding for fibronectin and type III collagen synthesis increased from the first day after operation and type I collagen synthesis increased from the second day after operation, as demonstrated by Northern hybridizations. Maximal mRNA production for fibronectin and collagens was seen at 2 and 7 days, respectively, after anastomosis. Activation of type I and III collagen genes in the anastomotic area was confined to tissues developing in the anastomotic line, the serosal surface and the submucosal layer. Strong fibronectin expression was observed in the same areas. The results suggest that genetic events leading to collagen synthesis in the anastomotic area start immediately after surgery. Maximal gene expression is not reached until 1 week after surgery.

Anastomosis, Surgical↗

PubMed1998

Transcriptional analysis of the Bordetella alcaligin siderophore biosynthesis operon.

The alc gene cluster of Bordetella pertussis includes three genes, alcA, alcB, and alcC, which are involved in alcaligin siderophore biosynthesis in response to iron starvation. The production of AlcA, AlcB, and AlcC in Bordetella cells and the transcriptional organization of alcA, alcB, and alcC were investigated by using a set of three alc'-'lacZ gene fusion constructs that were contiguous with the known promoter upstream of alcA and extended to fusion junctions within each alc cistron. All three alc'-'lacZ fusions exhibited iron-repressible reporter gene expression which was abolished by deletion of the 105-bp alcA promoter-operator region. In an immunoblot analysis using a monoclonal antibody specific for beta-galactosidase, the AlcA-LacZ, AlcB-LacZ, and AlcC-LacZ hybrid proteins were detected in Bordetella cells grown under iron-depleted conditions. A B. pertussis mutant in which the 105-bp alcA promoter-operator region was deleted by allelic exchange was unable to produce detectable levels of siderophore. Hybridization analysis using gene-specific probes showed that alc-specific transcript levels in the mutant were negligible compared with those of the wild-type parent. These results confirm that alcA, alcB, and alcC are cotranscribed from an iron-regulated control region immediately upstream of alcA. Transcript analysis using hybridization probes representing regions downstream of alcC demonstrated that alc transcription extends approximately 3.6 kb further downstream from the alcC coding region, suggesting the cotranscription of additional, uncharacterized alcaligin system genes.

Bacterial Proteins↗

PubMed1997

Multiple transcribed elements control expression of the Escherichia coli btuB gene.

Repression by vitamin B12 of the cobalamin transport protein BtuB in the outer membrane of Escherichia coli operates at both the transcriptional and translational levels and is controlled by transcribed sequences within the leader and proximal portion of the btuB coding sequence. The effects of deletions from either end of this region on repression and expression were determined with lac fusions. An element at the 5' end of the transcript and the putative attenuator within the coding sequence were required for transcriptional repression. The presence of either element caused a marked reduction in btuB-lacZ expression which was reversed by the presence of a conserved sequence element in the leader, suggesting the importance of long-range interactions in the btuB leader for expression and regulation.

Bacterial Outer Membrane Proteins↗

PubMed1995

Evidence of post-transcriptional regulation of L-selectin gene expression in rat lymphoid cells.

Early investigations of lymphocyte migration in the rat operationally identified a lymphocyte membrane protein, designated 'A.11', which mediates lymphocyte adherence to lymph node (LN) high endothelial venules (HEV). To determine the primary structure of A.11 and examine its expression in lymphoid cells, we constructed an expression phage cDNA library of rat thoracic duct lymphocytes (TDL) and performed screening by immunoselection (utilizing an anti-A.11 polyclonal antiserum) as well as by hybridization selection. We have isolated a approximately 1.6 kb clone, RS-2, and sequencing revealed that it encodes rat L-selectin. The clone contains the complete coding sequence, a 105-bp 5' untranslated region and a 359-bp 3' untranslated region. Transfection of RS-2 cDNA into 70Z/3 cells conferred binding to HEV concomitant with expression of A.11, providing direct evidence that A.11 is rat L-selectin. Metabolic radiolabelling studies revealed that thymocytes synthesize markedly less L-selectin than do TDL or LN lymphocytes. However, Northern blot studies using RS-2 as a probe indicate that thymocytes possess more L-selectin RNA than does TDL. Together, these data provide evidence that post-transcriptional events contribute to regulation of L-selectin expression in thymocytes.

Amino Acid Sequence↗

PubMedDate not supplied

Structure and expression of ribosomal protein genes in Xenopus laevis.

In Xenopus laevis, as well as in other vertebrates, ribosomal proteins (r-proteins) are coded by a class of genes that share some organizational and structural features. One of these, also common to genes coding for other proteins involved in the translation apparatus synthesis and function, is the presence within their introns of sequences coding for small nucleolar RNAs. Another feature is the presence of common structures, mainly in the regions surrounding the 5' ends, involved in their coregulated expression. This is attained at various regulatory levels: transcriptional, posttranscriptional, and translational. Particular attention is given here to regulation at the translational level, which has been studied during Xenopus oogenesis and embryogenesis and also during nutritional changes of Xenopus cultured cells. This regulation, which responds to the cellular need for new ribosomes, operates by changing the fraction of rp-mRNA (ribosomal protein mRNA) engaged on polysomes. A typical 5' untranslated region characterizing all vertebrate rp-mRNAs analyzed to date is responsible for this translational behaviour: it is always short and starts with an 8-12 nucleotide polypyrimidine tract. This region binds in vitro some proteins that can represent putative trans-acting factors for this translational regulation.

Animals↗

PubMed2001

Regulation of the steroid-inducible 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase gene in Comamonas testosteroni.

The Comamonas testosteroni 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase gene (hsdA) codes for an adaptive enzyme in the degradation of steroid compounds. However, no information was available on the molecular regulation of steroid-inducible genes nor on the mechanism of steroid signaling in procaryotes. We, therefore, investigated the cis- and trans-acting elements of hsdA expression to infer the mechanism of its molecular regulation by steroids. The gene was localized on a 5.257-kilobase EcoRI fragment of C. testosteroni chromosomal DNA. The promoter was characterized, and the transcriptional start site was identified. Two palindromic operator domains were found upstream of hsdA. A new gene coding for a trans-acting negative regulator (repressor A, RepA) of hsdA expression was characterized. The specific interaction between RepA, testosterone, and the operator domain is demonstrated. From our results we conclude that hsdA is under negative transcriptional control by an adjacent gene product (RepA). Accordingly, induction of hsdA by steroids in fact is a derepression, where steroidal inducers bind to the repressor, thereby preventing its binding to the hsdA operator.

Alcohol Oxidoreductases↗

PubMed1995

Inhibition of translation initiation on Escherichia coli gnd mRNA by formation of a long-range secondary structure involving the ribosome binding site and the internal complementary sequence.

Previous research has indicated that the growth rate-dependent regulation of Escherichia coli gnd expression involves the internal complementary sequence (ICS), a negative control site that lies within the 6-phosphogluconate dehydrogenase coding sequence. To determine whether the ICS acts as a transcriptional operator or attenuator, we measured beta-galactosidase-specific activities in strains carrying gnd-lac operon and protein fusions containing or lacking the ICS. Whereas the presence of the ICS repressed beta-galactosidase expression from a protein fusion by 5-fold during growth on acetate and by 2.5-fold during growth on glucose, it had no effect on beta-galactosidase expression from an operon fusion. In vitro ribosome binding experiments employing the primer extension inhibition (toeprint) assay demonstrated that the presence of the ICS in gnd mRNA reduces both the maximum extent and the rate of ternary complex formation. Moreover, the effects of deletions scanning the ICS on in vivo gene expression were highly correlated with the effects of the deletions on ribosome binding in vitro. In addition, the distal end of the ICS element was found to contribute more to ICS function than did the proximal portion, which contains the complement to the Shine-Dalgarno sequence. Finally, RNA structure mapping experiments indicated that the presence of the ICS in gnd mRNA reduces the access of the nucleotides of the ribosome binding site to the single-strand-specific chemical reagents dimethyl sulfate and kethoxal. Taken together, these data support the hypothesis that the role of the ICS in the growth rate-dependent regulation of gnd expression is to sequester the translation initiation region into a long-range mRNA secondary structure that blocks ribosome binding and thereby reduces the frequency of translation initiation.

Acetates↗

PubMed1991

Poly(A) site choice in retroelements: deja vu all over again?

The primary transcripts encoded by retroelements contain two polyadenylation [poly(A)] sites, positioned 5' and 3' of the protein-coding sequences. To ensure efficient gene expression in these systems, a mechanism must operate that suppresses use of the 5' site, enhances use of the 3' site, or both. These possibilities have been examined in a recent series of experiments that have revealed two main regulatory themes. First, maximum 3' end processing can require sequences other than core poly(A) signals, which are transcribed only before the 3' site. Second, processing is partly inhibited when the site is positioned close to the promoter. These results should serve as the basis for a more detailed understanding of how the choice of the poly(A) site is regulated in these elements.

Base Sequence↗

PubMed2024

Serum lncRNA ITGB2-AS1 and ICAM-1 as novel biomarkers for rheumatoid arthritis and osteoarthritis diagnosis.

BACKGROUND: The complete circulating long non-coding RNAs (lncRNAs) signature of rheumatoid arthritis (RA) and osteoarthritis (OA) is still uncovered. The lncRNA integrin subunit beta 2 (ITGB2)-anti-sense RNA 1 (ITGB2-AS1) affects ITGB2 expression; however, there is a gap in knowledge regarding its expression and clinical usefulness in RA and OA. This study investigated the potential of serum ITGB2-AS1 as a novel diagnostic biomarker and its correlation with ITGB2 expression and its ligand intercellular adhesion molecule-1 (ICAM-1), disease activity, and severity in RA and primary knee OA patients. SUBJECTS: Forty-three RA patients, 35 knee OA patients, and 22 healthy volunteers were included. RESULTS: Compared with healthy controls, serum ITGB2-AS1 expression was upregulated in RA patients but wasn't significantly altered in knee OA patients, whereas serum ICAM-1 protein levels were elevated in both diseases. ITGB2-AS1 showed discriminative potential for RA versus controls (AUC = 0.772), while ICAM-1 displayed diagnostic potential for both RA and knee OA versus controls (AUC = 0.804, 0.914, respectively) in receiver-operating characteristic analysis. In the multivariate analysis, serum ITGB2-AS1 and ICAM-1 were associated with the risk of developing RA, while only ICAM-1 was associated with the risk of developing knee OA. A panel combining ITGB2-AS1 and ICAM-1 showed profound diagnostic power for RA (AUC = 0.9, sensitivity = 86.05%, and specificity = 91.67%). Interestingly, serum ITGB2-AS1 positively correlated with disease activity (DAS28) in RA patients and with ITGB2 mRNA expression in both diseases, while ICAM-1 positively correlated with ITGB2 expression in knee OA patients. CONCLUSION: Our study portrays serum ITGB2-AS1 as a novel potential diagnostic biomarker of RA that correlates with disease activity. A predictive panel combining ITGB2-AS1 and ICAM-1 could have clinical utility in RA diagnosis. We also spotlight the association of ICAM-1 with knee OA diagnosis. The correlation of serum ITGB2-AS1 with ITGB2 expression in both diseases may be insightful for further mechanistic studies.

Humans↗

PubMed1990

Effect of partial removal of frontal or parietal bone on concentrations of mRNAs coding for preprocholecystokinin and preprosomatostatin in rat neocortex.

Partial removal of the frontal or parietal bone increased concentrations of mRNAs coding for preprocholecystokinin and preprosomatostatin in rat parietotemporal cortex by more than 170 and 67%, respectively, when measured 3 days after the operation. The increases were independent of the anaesthetic agent used during the operation and were transient with a maximum usually observed 3 days after the operation. They occurred not only in areas close to or under the removed bone part, but also in more distant areas. Thus, removal of the frontal bone also enhanced levels of preprocholecystokinin- and preprosomatostatin-mRNA in the parietotemporal and occipital cortex. mRNA concentrations were increased in the inner as well as outer layers of the cortex. The possible experimental and pathophysiological implications of the observed changes in gene expression of both neuropeptides in neocortical neurons are discussed.

Animals↗

PubMed1990

Organization and transcription of Volvox histone-encoding genes: similarities between algal and animal genes.

The nucleotide sequences of two non-allelic histone H2A-H2B gene loci of the green alga Volvox carteri have been determined. Each locus contains a divergently arranged H2A-H2B gene pair. The encoded proteins differ in one (H2A) and 16 positions (H2B), respectively. The coding regions are separated by short intercistronic segments (256 bp and 298 bp) containing TATA boxes and a central tandem repeat of a conserved 20-bp element as the putative histone-specific transcription signals. The 3'-untranslated regions exhibit a characteristic 3'-palindrome and weakly conserved spacer elements. Transcription in one gene locus was shown to initiate 48 bp upstream from H2A and 59 bp upstream from H2B. Contrary to higher plants, V. carteri histone mRNAs are nonpolyadenylated. S1 mapping and Northern-blotting experiments indicated that V. carteri histone mRNAs are terminated at the 3'-palindrome by the same mechanism that operates in vertebrates and sea urchins.

Amino Acid Sequence↗