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Results for “operational RNA code”

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PubMed1989

Gene expression in regenerating liver in relation to cell proliferation and stress.

When hepatocyte proliferation is stimulated in the liver by partial hepatectomy, messenger RNAs coding for fibrinogen, actin, c-myc and topoisomerase I are rapidly accumulated. We distinguish an early phase of accumulation (0-3 h after partial hepatectomy) which is also observed after a sham operation for the four genes, and during inflammation produced by Freund's adjuvant in the case of fibrinogen and c-myc genes. The hepatic response to inflammation appears therefore to mimic events characteristic of the G0/G1 transition, such as the accumulation of the c-myc mRNA. The late phase of mRNA accumulation (beyond 3 h after partial hepatectomy) is typical of liver regeneration. The level of c-myc mRNA is transiently increased (20-fold over normal) 20 h after partial hepatectomy, that is, at the time of DNA synthesis. Topoisomerase-I mRNA level increases between 3 and 24 h after partial hepatectomy (5-10-fold over normal). These results suggest that accumulation of c-myc and topoisomerase-I mRNAs is associated with DNA replication in regenerating liver.

Actins↗

PubMed1998

ptGAs--genetic algorithms evolving noncoding segments by means of promoter/terminator sequences.

In this article we present work on chromosome structures for genetic algorithms (GAs) based on biological principles. Mainly, the influence of noncoding segments on GA behavior and performance is investigated. We compare representations with noncoding sequences at predefined, fixed locations with "junk" code induced by the use of promoter/terminator sequences (ptGAs) that define start and end of a coding sequence, respectively. As one of the advantages of noncoding segments a few researchers have identified the reduction of the disruptive effects of crossover, and we solidify this argument by a formal analysis of crossover disruption probabilities for noncoding segments at fixed locations. The additional use of promoter/terminator sequences not only enables evolution of parameter values, but also allows for adaptation of number, size, and location of genes (problem parameters) on an artificial chromosome. Randomly generated chromosomes of fixed length carry different numbers of promoter/terminator sequences resulting in genes of varying size and location. Evolution of these ptGA chromosomes drives the number of parameters and their values to (sub)optimal solutions. Moreover, the formation of tightly linked building blocks is enhanced by self-organization of gene locations. We also introduce a new, nondisruptive crossover operator emerging from the ptGA gene structure with adaptive crossover rate, location, and number of crossover sites. For experimental comparisons of this genetic operator to conventional crossover in GAs, as well as properties of different ptGA chromosome structures, an artificial problem from the literature is utilized. Finally, the potential of ptGA is demonstrated on an NP-complete combinatorial optimization problem.

Algorithms↗

PubMed1990

The Balbiani ring 3 gene in Chironomus tentans has a diverged repetitive structure split by many introns.

A set of approximately 15 secretory proteins is synthesized by the salivary gland cells in the midge Chironomus tentans. These proteins are secreted but do not form insoluble fibers until they are transported out of the gland lumen. A Balbiani ring (BR) gene family consisting of four genes (BR1, BR2.1, BR2.2 and BR6) have previously been shown to encode four of these proteins, sp-I a to d, with relative molecular weights of 1 x 10(6). Each BR gene contains an uninterrupted block in which about 100 repeats are tandemly arranged. The repeats are virtually identical and efficient homogenization mechanisms must operate within each block. Here we describe a new BR gene, the BR3 gene, which according to structural similarities may belong to the BR gene family, but at the same time exhibits a strikingly different structure. The gene encodes a 10.9 kb transcript that contains 38 introns and is spliced into a 5.5 kb mRNA. The mRNA is translated into a cysteine-rich 185 kDa major component of the gland secretion. The coding sequence in the gene is built from diverged repeats in which mainly the cysteine codons are preserved and the sequence is split by the introns into 17 to 678-bp long exons. The introns are located at defined positions in relation to the repeat structure. In sharp contrast to the uninterrupted array of identical repeats in the BR1-BR6 genes, the repeats in the BR3 gene are not efficiently homogenized and have diverged extensively from each other. We propose that the splitting of the repeat structure into variable sized exons prevents homogenizations dependent on unequal aligning of homologous sequences.

Amino Acid Sequence↗

PubMed2004

Assessment of microbial populations in methyl ethyl ketone degrading biofilters by denaturing gradient gel electrophoresis.

Denaturing gradient gel electrophoresis (DGGE) analysis of polymerase chain reaction-amplified genes coding for 16S rRNA was used to assess differences in bacterial community structure as a function of spatial location along the height of two biofilters used to treat a model waste gas stream containing methyl ethyl ketone (MEK). One of the laboratory-scale biofilters was operated as a conventional continuous-flow biofilter (CFB) and the other was operated as a sequencing batch biofilter (SBB). Both biofilters, inoculated with an identical starting culture and operated over a period lasting more than 300 days, received the same influent MEK concentration and same mass of MEK on a daily basis. The systems differed, however, in terms of the fraction of time during which contaminated air was supplied and the overall operating strategy employed. DGGE analysis indicated that microbial community structures differed as a function of height in each of the biofilters. The DGGE banding patterns also differed between the two biofilters, suggesting that operating strategies imposed on the biofilters imparted a sufficiently large selective pressure to influence microbial community structures. This may explain, in part, the superior performance of the SBB over the CFB during model transient loading conditions, and it may open new possibilities for purposely manipulating the microbial populations in biofilters treating gas-phase contaminants in a manner that leads to more favorable treatment performance.

Air Conditioning↗

PubMed1994

A composite intragenic silencer domain exhibits negative and positive transcriptional control of the bone-specific osteocalcin gene: promoter and cell type requirements.

The osteocalcin (OC) silencer is a unique example of exonic sequences contributing to negative transcriptional control of mammalian gene expression. In this paper we demonstrate, using a reporter transfection assay, that multiple elements reside within the OC +24/+151 domain. Thirty-fold repression is mediated by the +49/+104 fragment, experimentally relocated 3' of the poly(A) signal. Deletion of either the +49/+54 protein-coding sequence or the +98/+104 intronic part of this fragment results in loss of repression activity, suggesting a bipartite organization of the +49/+104 silencer. Of particular interest, we have mapped an antisilencer activity to the ACCCTCTCT motif (+40/+48), found in silencers associated with several other genes. Extension of the +49/+104 silencer to include the +24/+48 and/or the +105/+151 sequences results in increased silencer activity up to 170-fold, suggesting the presence of additional silencer elements within these sequences. The activity of the silencer contained within the +24/+151 OC sequence is directed to the basal promoter and is not dependent on 5' distal enhancer elements, including those that mediate responsiveness of OC transcription to vitamin D. The OC silencer represses the heterologous thymidine kinase promoter and is operative in osseous (normal diploid osteoblasts, ROS 17/2.8 osteosarcoma) as well as HeLa cells. Our results, which suggest the presence of at least five regulatory elements downstream of the OC transcription start site, indicate the complexity of sequences that mediate repression of OC promoter activity.

Base Sequence↗

PubMed1991

Targeting the Escherichia coli lac repressor to the mammalian cell nucleus.

We have previously shown that about 90% of total Escherichia coli lac repressor synthesized in mammalian cells is located in the cytoplasm [Hu and Davidson, Cell 48 (1987) 555-566]. To target a functional lac repressor to the nucleus, we mutated 10 nucleotides at the 3' end of the coding sequence, thus adding the nuclear localization signal of the simian virus 40 large-T antigen to the C terminus of the repressor. The mutant lacI gene and the wild-type (wt) gene, both in standard animal cell expression vectors, driven by the promoter of the Rous sarcoma virus long terminal repeat, were stably transfected into three rodent cell lines. In confirmation of our previous results, only about 10% of the wt repressor, but all of the mutant protein, was localized in the nucleus. DNase I footprint analyses showed that the mutant repressor retained the same operator DNA-binding specificity as wt repressor. Furthermore, both repressor-operator complexes could be dissociated by addition of isopropyl-beta-D-thiogalactopyranoside in vitro. However, the ratio of number of repressor molecules per nucleus that, by in vitro assay, could bind to the operator sequence to the number of monomer repressor polypeptides per nucleus, as determined by Western blotting, was about 1:4 for the wt repressor and about 1:30 for the mutant repressor. This suggests that: (a) the mutant repressor assembles into tetramers inefficiently; and/or (b) it has reduced binding affinity to the operator sequence; and/or (c) it has higher binding affinity to nonspecific DNA.

Antigens, Viral, Tumor↗

PubMed1994

PC12 variants deficient in norepinephrine transporter mRNA have wild type activities of several other related transporters.

Wild type PC12 pheochromocytoma cells express a Na(+)-dependent norepinephrine transporter that operates in the uptake of catecholamines. In addition to the previously described Na(+)-dependent system A for the uptake of alpha-amino-isobutyric acid and system Gly for glycine, we have identified two other Na(+)-dependent transporter systems for amino acid uptake in these cells: 1) system beta for beta-alanine and taurine; and 2) a system for creatine. Uptake of alpha-amino-isobutyric acid, glycine, beta-alanine, and creatine is not affected in some PC12 variants that were previously shown to be deficient in catecholamine uptake and to have decreased levels of norepinephrine transporter mRNA. We have isolated two PC12 cDNA clones that are essentially identical in sequence to recently reported cDNAs for rat brain taurine and creatine transporters, respectively, and a third cDNA that appears to code for a novel transporter. mRNAs for these three transporters are present at wild type levels in those variants that express no or little norepinephrine transporter mRNA. These results support the notion that the expression of catecholamine reuptake transporters may be particularly susceptible to down-regulation.

Amino Acids↗

PubMed1998

Structure and organization of the Drosophila cholinergic locus.

The Drosophila cholinergic locus is composed of two distinct genetic functions: choline acetyltransferase (ChAT; EC 2.3.1.6), the enzyme catalyzing biosynthesis of neurotransmitter acetylcholine (ACh), and the vesicular ACh transporter (VAChT), the synaptic vesicle membrane protein which pumps transmitter into vesicles. Both genes share a common first exon and the remainder of the VAChT gene contains a single coding exon residing entirely within the first intron of ChAT. RNase protection analysis indicates that all Drosophila VAChT specific transcripts contain the shared first exon and suggests common transcriptional control for ChAT and VAChT. Similar types of genomic organization have been evolutionarily conserved for cholinergic loci in nematodes and vertebrates, and may operate to ensure coordinate expression of these functionally related genes in the same cells. The relative levels of Drosophila ChAT and VAChT mRNA differ, however, in different tissues or in Cha mutants, indicating that independent regulation of ChAT and VAChT transcripts may occur post-transcriptionally. The predicted Drosophila VAChT protein is composed of 578 amino acids and contains 12 conserved putative transmembrane domains. Full-length VAChT cDNA is 7.2 kilobase long and has unusually long 5'- and 3'-untranslated regions (UTR). The 5'-UTR contains a GTG ChAT translational initiation codon along with three other potential ATG initiation codons. These features of the VAChT 5'-UTR region suggest that a ribosome scanning model may not be used for VAChT translation initiation.

Amino Acid Sequence↗

PubMed1990

Frequent activation of N-myc genes by hepadnavirus insertion in woodchuck liver tumours.

The recent finding of c-myc activation by insertion of woodchuck hepatitis virus DNA in two independent hepatocellular carcinoma has given support to the hypothesis that integration of hepatitis B viruses into the host genome, observed in most human and woodchuck liver tumours, might contribute to oncogenesis. We report here high frequency of woodchuck hepatitis virus DNA integrations in two newly identified N-myc genes: N-myc1, the homologue of known mammalian N-myc genes, and N-myc2, an intronless 'complementary DNA gene' or 'retroposon' that has retained extensive coding and transforming homology with N-myc. N-myc2 is totally silent in normal liver, but is overexpressed without genetic rearrangements in most liver tumours. Moreover, viral integrations occur within either N-myc1 or N-myc2 in about 20% of the tumours, giving rise to chimaeric messenger RNAs in which the 3' untranslated region of N-myc was replaced by woodchuck hepatitis virus sequences encompassing the viral enhancer. Insertion sites were clustered in a short sequence of the third exon that coincides with a retroviral integration hotspot within the murine N-myc gene, recently described in T-cell lymphomas induced by murine leukaemia virus. Thus, comparable mechanisms, leading to deregulated expression of N-myc genes, may operate in the development of tumours induced either by hepatitis virus or by nonacute retroviruses in rodents. Activation of myc genes by insertion of hepadnavirus DNA now emerges as a common event in the genesis of woodchuck hepatocellular carcinoma.

Amino Acid Sequence↗

PubMed1992

Cardiac hypertrophy-induced changes in mRNA levels for TGF-beta 1, fibronectin, and collagen.

Cardiac hypertrophy induced by pressure overload is accompanied by increases in the deposition of extracellular matrix (ECM) proteins. We wanted to determine in this study whether changes in mRNA coding for transforming growth factor (TGF)-beta 1, TGF-beta 3, and the ECM proteins, fibronectin and collagen, occur during the early phases of cardiac hypertrophy. Steady-state mRNA levels were determined in sham-operated and thoracic-banded hypertrophied rat myocardium from 6 h to 30 days after surgery. TGF-beta 1 mRNA increased significantly (1.7-fold vs. control) 12 h after aortic banding, decreasing to control levels by 14 days. No significant changes were observed for TGF-beta 3 message. Fibronectin mRNA levels increased twofold at day 1 and peaked to approximately threefold at day 3. Type I and III collagen mRNA expression was similar to control levels at day 1 but increased significantly 3 days after banding. Cardiac hypertrophy also resulted in an induction of mRNA for an embryonic isoform of fibronectin (EIIIA+) that is generated through alternative splicing of the gene. These findings indicate that, with myocardial hypertrophy, mRNAs for fibronectin are increased as early as 1 day after banding, which may allow for an initial increase in the production of fibronectin followed by the deposition of collagen. These increased mRNA levels for the ECM proteins are preceded by marked increases in TGF-beta 1 mRNAs.

Animals↗

PubMed2004

A molecular code for splicing silencing: configurations of guanosine-rich motifs.

Alternative pre-mRNA splicing is frequently used to expand the protein-coding capacity of genomes, and to regulate gene expression at the post-transcriptional level. It is a significant challenge to decipher the molecular language of tissue-specific splicing because the inherent flexibility of these mechanisms is specified by numerous short sequence motifs distributed in introns and exons. In the present study, we employ the glutamate NMDA (N-methyl-D-aspartate) R1 receptor (GRIN1) transcript as a model system to identify the molecular determinants for a brain region-specific exon silencing mechanism. We identify a set of guanosine-rich motifs that function co-operatively to regulate the CI cassette exon in a manner consistent with its in vivo splicing pattern. Whereas hnRNP (heterogeneous nuclear ribonucleoprotein) A1 mediates silencing of the CI cassette exon in conjunction with the guanosine-rich motifs, hnRNP H functions as an antagonist to silencing. Genome-wide analysis shows that, while this motif pattern is rarely present in human and mouse exons, those exons for which the pattern is conserved are generally found to be skipped exons. The identification of a similar arrangement of guanosine-rich motifs in transcripts of the hnRNP H family of splicing factors has implications for their co-ordinate regulation at the level of splicing.

Alternative Splicing↗

PubMed1991

Colocalization of neurotransmitters analyzed by in situ hybridization.

In situ hybridization and Northern blot analysis has been used to analyse in some detail the localization and regulation of the messenger molecules adrenaline, noradrenaline and neuropeptide tyrosine (NPY) within cells of the sympathetic nervous system and the adrenal medulla. In the rat adrenal gland, a novel NPY containing population of ganglion cells was found. Synthetic oligonucleotide probes complementary to mRNA coding for the catecholamine synthesizing enzymes phenylethanolamine N-methyltransferase (PNMT), tyrosine hydroxylase (TH) and NPY were used to analyse the regulation of these genes following administration of the catecholamine depleting drug reserpine. Twenty-four hours after a single dose of reserpine, a differential regulation of PNMT, TH and NPY was found. Thus, a dramatic decrease in PNMT mRNA was observed in the adrenal medulla. In contrast, mRNA for both TH and NPY exhibited an increase. Different regulatory mechanisms may thus operate for these three compounds coexisting in chromaffin cells of the adrenal medulla. The regulation of enzymes and peptides was also studied in human sympathetic ganglia. After brief electrical preganglionic stimulation of thoracic ganglia in humans, in situ hybridization was performed with synthetic oligonucleotide probes complementary to TH, dopamine beta-hydroxylase (DBH) and NPY mRNA respectively. A several fold increase in all three mRNAs was found in the principal ganglion cells. The results point to a very rapid regulation of genes involved in signal transmission in the sympathetic nervous system of humans. The results also suggest a novel way to define neuronal projections by visualizing increases in mRNA levels following electrical stimulation.

Adrenal Glands↗

PubMed1993

Interlocked circle formation by group I introns: structural requirements and mechanism.

Precursor RNA transcribed from the yeast mitochondrial gene coding for the large ribosomal RNA contains a group I intron that can excise itself in vitro. Apart from group I specific sequence elements the intron also contains a gene encoding a DNA endonuclease involved in intron dispersal. A precursor RNA derivative from which this gene has been removed self-splices efficiently, but due to activation of cryptic opening sites located in the 5' exon, the 3' part of this exon is sometimes co-excised with the intron. Upon further reaction, this enlarged intron molecules give rise to interlocked circles, comprising small circles derived from 5' exon parts and large circles of the intron. Sequence comparison between cryptic opening sites and authentic splice sites reveals in most cases homology with the 3' exon part that is capable of interacting with the Internal Guide Sequence. The role of the IGS was further substantiated by replacing the cryptic opening sites with well defined sequences of authentic splice sites: one corresponding to the 3' splice site and its mutant derivatives, the other to a fragment containing the natural 5'-3' exon junction. Precursor RNAs derived from these constructs give rise to interlocked circles, and mutation studies confirm that the 3' exon nucleotides flanking a 3' splice site are essential for their formation. The results underline the crucial role of the IGS in interlocked circle formation which behaves similarly as in the normal self-splicing reactions. It has been proposed that the two short helices formed by basepairing of the IGS with the 5' and 3' exon can co-axially stack on top of each other forming a quasi continuous RNA double helix or pseudoknot. We present a model explaining how transesterification reactions of a mutant precursor RNA in such a pseudoknot can lead to interlocked circles. The experiments support the notion that a similar structure is also operative in splicing of wild type precursor RNA.

Base Sequence↗

PubMed1988

Search for a scrapie-specific nucleic acid: a progress report.

Scrapie agent contains a proteinaceous component as well as an 'informational' molecule (suggested by the existence of distinct strains of scrapie). These operationally defined entities may be the same molecule, an infectious protein, or distinct, in which case a nucleic acid might encode the genetic information. Purification of scrapie agent enriched a protein, PrPSc, by virtue of its relative protease resistance. There is only a single PrP gene and the primary translation product of PrP mRNA is the same in normal and scrapie-infected brain; therefore the normal PrPC and the protease-resistant isoform, PrPSc, found in scrapie, probably result from different post-translational events. To search for scrapie-specific nucleic acid, globin RNA made in vitro was added to highly purified infectious preparations at a ratio of 10(3) molecules per infectious unit, nucleic acids were isolated and denatured, and cDNA synthesized using random oligonucleotide primers. Clones containing globin-related sequences were identified by in situ hybridization. 150 plaques not hybridizing to the globin probe were isolated. Inserts larger than 50 base pairs were analysed. By hybridization to a globin probe at reduced stringency all but four clones were found to contain small globin related inserts; two of these hybridized to hamster repetitive sequences as shown by Southern blot analysis. The other clones not related to hamster nucleic acids may be derived from unknown sources of contamination or from scrapie-specific nucleic acids.

Animals↗

PubMed1998

Variation in the glycoprotein and VP35 genes of Marburg virus strains.

Marburg virus, the prototype of the family Filoviridae, differs genetically, serologically, and morphologically from Ebola viruses. To better define the genetic variation within the species, VP35 and glycoprotein (GP) genes of representative human isolates from four known episodes of Marburg virus hemorrhagic fever were analyzed. The percentage nucleotide differences in the GP gene coding regions of Marburg viruses (0.1-21%) was nearly equal to the percentage amino acid changes (0-23%), while the percentage nucleotide differences in VP35 coding regions (0.3-20.9%) were higher than the percentage amino acid changes (0.9-6.1%), indicating a greater number of nonsynonymous changes occurring in the GP gene. The higher variation in the GP gene and the corresponding protein, especially those changes in the variable middle region of the GP, suggests that the variability may be the result of responses to natural host pressures. Analysis of the GP gene open reading frame shows a nonrandom distribution of nonsynonymous mutations that may indicate positive Darwinian selection is operating within the variable region. A heptad repeat region and an adjoining predicted fusion peptide are found in the C-terminal third of Marburg virus GPs, as has been previously shown for Ebola virus, and are similar to those found in transmembrane glycoproteins of retroviruses, paramyxoviruses, coronaviruses, and influenza viruses. Comparative analyses showed that there are two lineages within the Marburg virus species of filoviruses. The most recent isolate from Kenya (1987) represents a separate genetic lineage within the Marburg virus species (21-23% amino acid difference). However, this lineage likely does not represent a separate Marburg subtype, as the extent of divergence is less than that separating Ebola virus subtypes.

Amino Acid Sequence↗

PubMed1989

[Left ventricular accumulation of messenger ribonucleic acid coding for the natriuretic atrial factor in various experimental models of cardiac hypertrophy in rats].

Cardiac hypertrophy secondary to chronic hemodynamic overload is associated with an increase in the ventricular concentration of the messenger ribonucleic acid (mRNA) coding for the atrial natriuretic factor (ANF). We have compared, in male Wistar rats (10 week old, 200-220 g), using dot blot hybridization and a specific oligonucleotide probe, the left ventricular concentration of ANF mRNA (LV ANF mRNA) in 4 models of chronic hemodynamic overload inducing various patterns of left ventricular hypertrophy (LVH): a model of volume overload, the aortocaval fistula (ACF, n = 15); a model of pressure overload, coarctation of the abdominal aorta (CoA, n = 13) and 2 models of mixed overload, aortic regurgitation (AR, n = 7) and myocardial infarction (INF, n = 18). A month after surgery, LVH was 49 p. 100 for AR, 41 p. 100 for Co A and 21 p. 100 for ACF. Instead of a severe infarction, LVH was 6 p. 100 in INF demonstrating a marked hypertrophy of the non infarcted myocardium. For each model, LV ANF mRNA was compared to that in a corresponding group of sham-operated control rats and expressed as the percentage of ANF mRNA concentration in the pooled atria of the controls. In the 4 control groups LV ANF mRNA was 1 +/- 0.5 p. 100 that in the corresponding atria and the sham-operated animals were thus pooled in a single group (n = 19). In the 4 models of LVH, LV ANF mRNA markedly increased as compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2005

Developmentally regulated instability of the GPI-PLC mRNA is dependent on a short-lived protein factor.

The expression of the vast majority of protein coding genes in trypanosomes is regulated exclusively at the post-transcriptional level. Developmentally regulated mRNAs that vary in levels of expression have provided an insight into one mechanism of regulation; a decrease in abundance is due to a shortened mRNA half-life. The decrease in half-life involves cis-acting elements in the 3' untranslated region of the mRNA. The trans-acting factors necessary for the increased rate of degradation remain uncharacterized. The GPI-PLC gene in Trypanosoma brucei encodes a phospholipase C expressed in mammalian bloodstream form, but not in the insect procyclic form. Here, it is reported that the differential expression of the GPI-PLC mRNA also results from a 10-fold difference in half-life. Second, the instability of the GPI-PLC mRNA in procyclic forms can be reversed by the inhibition of protein synthesis. Third, specifically blocking the translation of the GPI-PLC mRNA in procyclic forms by the inclusion of a hairpin in the 5' untranslated region does not result in stabilization of the mRNA. Thus, the effect of protein synthesis inhibitors in stabilizing the GPI-PLC mRNA operates in trans through a short-lived factor dependent on protein synthesis.

Animals↗

PubMed1986

Genetic definition of the translational operator of the threonine-tRNA ligase gene in Escherichia coli.

The Escherichia coli gene thrS that codes for threonine-tRNA ligase (tRNAThr ligase, formerly threonine-tRNA synthetase, EC 6.1.1.3) has previously been shown to be negatively autoregulated at the level of translation. Here we describe the use of several thrS-lac gene fusions to isolate cis-acting regulatory mutations that increase the translation but not the transcription of the thrS gene. These mutations lead to a total loss of control of repression and derepression of thrS. DNA sequence analysis locates the mutations between 10 and 40 base pairs upstream of the translation initiation codon of thrS and more than 100 base pairs downstream of the transcription initiation site. The mRNA region where these mutations are located shares primary and secondary structure homologies with specific parts of several isoacceptor tRNAThr species. These findings suggest that the ligase regulates its translation by binding to its mRNA at a place that shares some homology with its natural substrate.

Amino Acyl-tRNA Synthetases↗