Inter-kingdom DNA transfer decoded.
Explore the source record for details and available documents.
Agrobacterium tumefaciens↗
SEARCH · PubMed Health
Results for “deCode Genetics”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The Potential Link Between Eosinophilic Esophagitis and Food Allergy: Inflammatory Pathogenesis and Management.
Eosinophilic esophagitis (EoE) has transitioned from an isolated gastrointestinal disorder to a recognized type 2 immune-mediated allergic disease, most likely representing a late manifestation of the atopic march. This comprehensive review examines the complex inflammatory pathogenesis linking EoE and food allergy, and critically discusses the mechanisms of disease induction, dietary treatments, and emerging clinical challenges. While genome-wide association studies identify shared susceptibility loci with classic atopy, EoE exhibits distinct tissue-specific pathways, particularly dominated by the local interleukin (IL)-13 axis and highly esophagus-selective proteases like Calpain-14. This unique immunological interplay is clinically epitomized by food oral immunotherapy (OIT)-induced EoE. During OIT, systemic immune reprogramming successfully drives immune tolerance-marked by a robust increase in plasma food-specific IgG4-but fails at the local level, due to the persistence of pathogenic Th2 cells and aberrant mucosal IgG4 immune complex deposition within the esophageal lamina propria. Regarding therapeutic management, conventional skin and serum allergy testing remain highly inaccurate in identifying dietary triggers, rendering test-guided diets ineffective. Conversely, empiric elimination diets achieve robust histological remission, ranging from standardized six-food restrictions to pragmatic single-food approaches targeting cow's milk. Furthermore, novel insights into industrial milk processing (such as UHT sterilization and homogenization) and specific beta-casein genetic variants (A1 vs A2) highlight how altered protein structures generate neoantigens that accelerate esophageal immunogenicity. In conclusion, decoding the divergent immunological mechanisms operating in the refractory esophagus is essential to move beyond trial-and-error dietary interventions towards non-invasive monitoring tools, precision medicine, and optimized biological therapies in EoE management.
Calpain14↗
Comparison of X-ray crystal structure of the 30S subunit-antibiotic complex with NMR structure of decoding site oligonucleotide-paromomycin complex.
Aminoglycoside antibiotics that bind to 16S ribosomal RNA in the aminoacyl-tRNA site (A site) cause misreading of the genetic code and inhibit translocation. Structures of an A site RNA oligonucleotide free in solution and bound to the aminoglycosides paromomycin or gentamicin C1a have been determined by NMR. Recently, the X-ray crystal structure of the entire 30S subunit has been determined, free and bound to paromomycin. Distinct differences were observed in the crystal structure, particularly at A1493. Here, the NMR structure of the oligonucleotide-paromomycin complex was determined with higher precision and is compared with the X-ray crystal structure of the 30S subunit complex. The comparison shows the validity of both structures in identifying critical interactions that affect ribosome function.
Anti-Bacterial Agents↗
Genetic and epigenetic alterations of 9p21 gene products in benign and malignant tumors of the head and neck.
The multistep process of tumorigenesis has not been decoded to date, although numerous investigations into probable molecular changes have meanwhile been conducted. However, not only DNA changes or loss of alleles cause deregulation of gene function, but also epigenetic alterations (e.g. methylation) result in functional loss. The INK4a-ARF (CDKN2A) locus, located on chromosome 9p21, encodes two functionally distinct tumor suppressor genes, p14ARF and p16INK4a, which play active roles in the p53 and Rb tumor suppressive pathways. We therefore examined not only p16 and p14 proteins, but also alterations of the INK4a-ARF locus, including methylation and loss of heterozygosity in benign and malignant tumors of the head and neck (squamous cell carcinomas and pleomorphic adenomas). In benign pleomorphic adenomas, methylation of p14ARF was found in 1 out of 42 (2%) cases, whereas alterations of p16INK4a occurred in 12/42 (29%) pleomorphic adenomas. In HNSCC, methylation of p16INK4a occurred in 16 out of 50 (32%) carcinomas. P14ARF was found to be methylated in 8 out of 50 cases (16%). Our results demonstrate that alterations of the INK4a-ARF locus are frequent and important events not only in the carcinogenesis of malignant, but also in benign tumors.
Adenoma, Pleomorphic↗
Genetic evidence against the 16S ribosomal RNA helix 27 conformational switch model.
A mechanistic understanding of ribosome function demands knowledge of the conformational changes that occur during protein synthesis. One current model proposes a conformational switch in Helix 27 (H27) of 16S rRNA involved in the decoding of mRNA. This model was based on the behavior of mutations in the 912 region of H27 of Escherichia coli 16S rRNA, which were predicted to stabilize the helix in either of two alternative conformations. This interpretation was supported by evidence from both genetics and structural biochemistry. However, recently published X-ray crystallographic structures of the Thermus thermophilus 30S subunit at different stages of tRNA selection have raised doubts regarding the validity of this model. We have therefore revisited the model genetically by constructing a H27 quadruple mutation (C912G, C910G, G885C, and G887C), which would create multiple mismatches in the proposed alternative conformation without perturbing the native H27 conformation seen in the crystal structures. Inconsistent with the H27 switch model, cells containing pure populations of quadruple mutant ribosomes grow at essentially wild-type rates. The mutants used to construct the H27 switch model all carried A2058G in 23S rRNA and C1192U in 16S rRNA as selectable markers. The quadruple mutant carrying these additional marker mutations is deleterious, and we conclude that they have a synergistic effect when combined with other mutations and are not phenotypically silent. Their presence confounded the interpretation of the original mutant phenotypes and, in light of the viability of the quadruple mutant, we conclude that the genetic evidence no longer supports the model.
Anti-Bacterial Agents↗
Signals determining translational start-site recognition in eukaryotes and their role in prediction of genetic reading frames.
A special methionyl-tRNA (RNAi) is universally required to initiate translation. The conversation of this reactant throughout evolution, as well as its unusual decoding properties, suggested an alternate mechanism for tRNA-mRNA interactions at initiation. We have reported that the sequence of bases neighboring the start codons of many eubacterial genes are complementary not only to the 16S rRNA 3' end and to the anticodon of tRNAi, but, also, have the potential to base-pair the D, T or extended anticodon loops of this tRNAi. The coding properties of tRNAi and mutations that affect translation suggest that these signals may function. This hypothesis explains the observation that unusual triplets can start prokaryotic and mitochondrial genes and predicts the occurrence of other reading frames. Furthermore, it suggests a unifying model of chain initiation based on RNA-RNA contacts and displacements. Here we examine the start domain of 290 eukaryotic genes for their ability to base-pair the tRNAi loops and the 18S rRNA. We observe that both methionine start, and methionine coding regions have the potential to pair with the 18S rRNA, but that the nucleotide distribution about start codons strongly favoured such pairings over that near internal AUGs. The 5' extended anticodon of tRNAi is methylated, and was not represented in the mRNA with high frequency. However, the tetramer AUGg did occur with high frequency in the start domain. A modification of the tRNAi T loop also decreases its base-pairing potential. Interestingly, complementarity to the T loop did not occur with high frequency in the start sites. The early coding region, 10 to 34 nucleotides 3' to the initiator AUG, is complementary to the tRNAi D loop in many cases, while no such affinity is found near internal AUGs. The nucleotides around initiator AUGs were heavily biassed toward the sequence gccaccAUGgcg. No such tendency was noted around internal AUGs. Although the role of this sequence bias is unclear, the sequence gccaccAUGg has been shown by Kozak to promote initiation. Another distinguishing feature was a C-rich tract 7 to 34 nucleotides 5' to the initiator AUGs. Ability to pair with more than eight bases of the start consensus sequence, matching of 6 or 7 nucleotides to the D loop on the 3' side, an C-richness on the 5' side were used as criteria for distinguishing start AUGs.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Early development of children at familial risk for dyslexia--follow-up from birth to school age.
We review the main findings of the Jyväskylä Longitudinal study of Dyslexia (JLD) which follows the development of children at familial risk for dyslexia (N = 107) and their controls (N = 93). We will illustrate the development of these two groups of children at ages from birth to school entry in the skill domains that have been connected to reading and reading disability in the prior literature. At school entry, the highest score on the decoding task among the poorer half (median) of the at risk children--i.e. of those presumably being most likely genetically affected--is 1 SD below the mean of the control group. Thus, the familial risk for dyslexia shows expected consequences. Among the earliest measures in which group differences as well as significant predictive associations with the first steps in reading have emerged, are indices of speech processing in infancy. Likewise, various measures of early language including pronunciation accuracy, phonological, and morphological skills (but not performance IQ) show both group differences and predictive correlations, the majority of which become stronger as the reliability of the measures increases by age. Predictive relationships tend to be strong in general but higher in the at risk group because of its larger variance in both the predictor variables and in the dependent measures, such as early acquisition of reading. The results are thus promising in increasing our understanding needed for early identification and prevention of dyslexia.
Child↗
Were RNA replication and translation directly coupled in the RNA (+protein?) World?
The ribosome is proposed to have evolved from an ancestor that simultaneously replicated and translated template RNA. At its decoding site, this ancestor to the ribosome carried a ribozyme that assembled product RNA by sequentially ligating anticodon triplets excised from tRNAs. This ribozyme was the ancestor of the Group I introns, which are still present on some ribosomal RNA precursors. Coupling of reversible RNA replication by transesterification with the thermodynamically favourable process of transpeptidation provides a rationale for the evolution of the complete ribosome as a replicase for large RNAs in the RNA (+protein?) world. A detailed and experimentally verifiable mechanism can be proposed for simultaneous replication and translation. Sequence requirements for recognition of the decoding complex as a substrate helix by these ribozymes are consistent with earlier models for the origin of the genetic code, but require an indirect mode for ribosomal self-replication. This proposal has the potential to explain the location of Group I introns in the anticodon loops of some tRNAs.
Animals↗
Tradescantia stamen hair mutation bioassay.
The Tradescantia stamen hair mutation (Trad-SH) assay (clone 4430) was evaluated for its efficiency and reliability as a screen for mutagens in an IPCS collaborative study on plant systems. Four coded chemicals, i.e. azidoglycerol (AG, 3-azido-1,2-propanediol), N-methyl-N-nitrosourea (MNU), sodium azide (NaN3) and maleic hydrazide (MH) were distributed by the Radian Corporation to the five laboratories in five different countries for testing mutagenicity. Pink mutations were scored between the 7th and 14th day according to a standard protocol. Test results from the five individual laboratories were analyzed and compared after decoding. One out of the two laboratories that conducted tests on AG demonstrated that AG is a mutagen with genetically effective doses ranging from 50 to 100 micrograms/ml. MH yielded positive responses in all laboratories but no linear dose-response pattern was observed. The effective dose range for MH was between 1 and 45 micrograms/ml. The mutagenicity of MNU was reported by five laboratories in the dose range between 10 and 80 micrograms/ml. NaN3, which exhibited a relatively high degree of toxicity, elicited a positive mutagenic response in three of the five laboratories in which it was tested. As with MNU the effective dose for NaN3 ranged between 3 and 80 micrograms/ml. The results from the current study substantiate the Trad-SH assay as a reliable system for screening chemicals for their potential mutagenic effects. Although the study was carried out exclusively under laboratory conditions, a survey of the current literature would indicate that the Trad-SH assay could be an effective in situ monitor of gaseous, liquid, and radioactive pollutants as well.
Azides↗
Plant U-box E3 ligases: Versatile regulators of environmental stress adaptation and ABA signaling.
Ubiquitination is a reversible post-translational modification that orchestrates a wide spectrum of fundamental processes throughout the plant life cycle. Executed by a hierarchical E1-E2-E3 cascades, this modification tags targets with ubiquitin to modulate their turnover, activity, or subcellular compartmentalization. Among the diverse E3 ligase families, plant U-box (PUB) proteins stand out as a prominent class that determines substrate selection and has emerged as a focal point of stress biology. In this review, we first delineate the structural features of PUB proteins, highlighting their conserved domains and associated regulatory motifs. We then systematically dissect their multifaceted functions in abiotic stress adaptation, encompassing drought, salinity, extreme temperatures, oxidative stress, heavy metal toxicity, with particular emphasis on their integration with ABA signaling networks. We further outline critical knowledge gaps and propose future strategies to decode the regulatory architecture of PUBs. Collectively, this review provides a theoretical foundation and new insights for facilitating the genetic improvement of crop resilience in the face of continuously intensifying environmental stresses through the manipulation of PUB-mediated ubiquitination networks.
ABA signaling↗
Conformational analysis of Escherichia coli 30S ribosomes containing the single-base mutations G530U, U1498G, G1401C, and C1501G and the double-base mutation G1401C/C1501G.
Biochemical and genetic studies have pointed out the importance of several sites in 16S ribosomal RNA of Escherichia coli in the decoding process. These sites consist of the core of the decoding center (1400/1500 region) and two other segments (530 and 1050/1200 regions). To detect a possible structural link between these functionally related regions, we analyzed their sensitivity to conformational changes induced by mutations which are located in each of these regions and are known to affect the decoding process. The conformations of five segments of 16S rRNA (1-106, 406-569, 780-978, 997-1247, and 1334-1519) were analyzed by chemical probing of 30S ribosomes containing the following mutations: G530U, U1498G, G1401C, C1501G, and G1401C/C1501G. Ribosomes reconstituted with natural wild-type 16S RNA showed only minor conformational differences with respect to ribosomes isolated from cells. When 16S RNA made in vitro replaced natural 16S RNA, a slightly looser conformation of the central core region was found. Mutant ribosomes made by reconstitution with mutant 16S RNA made in vitro showed conformational effects which were in all cases localized to the region of secondary structure surrounding the site of mutation. Although the core of the decoding center (1400/1500 region) and the two other sites (530 and 1050/1200 regions) participating in the decoding function have been functionally linked, our data indicate that they are structurally independent. They also provide evidence for an unusual structure of the 1400/1500 decoding center, possibly involving noncanonical interactions. Furthermore, the absence of any conformational effect induced by the G530U mutation except at the site of mutation itself points to its direct, as opposed to indirect, involvement in the decoding function of the ribosome.
Base Sequence↗
Genetic analysis identifies a function for the queC (ybaX) gene product at an initial step in the queuosine biosynthetic pathway in Escherichia coli.
Queuosine (Q), one of the most complex modifications occurring at the wobble position of tRNAs with GUN anticodons, is implicated in a number of biological activities, including accuracy of decoding, virulence, and cellular differentiation. Despite these important implications, its biosynthetic pathway has remained unresolved. Earlier, we observed that a naturally occurring strain of Escherichia coli B105 lacked Q modification in the tRNAs. In the present study, we developed a genetic screen to map the defect in E. coli B105 to a single gene, queC (renamed from ybaX), predicted to code for a 231-amino-acid-long protein with a pI of 5.6. As analyzed by mobility of tRNA(Tyr) on acid urea gels and two-dimensional thin-layer chromatography of the modified nucleosides, expression of QueC from a plasmid-borne copy confers a Q+ phenotype to E. coli B105. Further, analyses of tRNA(Tyr) from E. coli JE10651 (queA mutant), its derivative generated by deletion of chromosomal queC (queA deltaqueC), and E. coli JE7325, deficient in converting preQ0 to preQ1, have provided the first genetic evidence for the involvement of QueC at a step leading to production of preQ0, the first known intermediate in the generally accepted pathway that utilizes GTP as the starting molecule. In addition, we discuss the possibilities of collaboration of QueC with other cellular proteins in the production of preQ0.
Amino Acid Sequence↗
Recessive lethality of yeast strains carrying the SUP61 suppressor results from loss of a transfer RNA with a unique decoding function.
Explore the source record for details and available documents.
Base Sequence↗
Codon recognition and decoding: the transorientation hypothesis.
Explore the source record for details and available documents.
Anticodon↗
[Molecular study on decoding of memory].
Explore the source record for details and available documents.
Adaptor Proteins, Signal Transducing↗
Adaptation of an orthogonal archaeal leucyl-tRNA and synthetase pair for four-base, amber, and opal suppression.
Recently, it has been shown that an amber suppressor tRNA/aminoacyl-tRNA synthetase pair derived from the tyrosyl-tRNA synthetase of Methanococcus jannaschii can be used to genetically encode unnatural amino acids in response to the amber nonsense codon, TAG. However, we have been unable to modify this pair to decode either the opal nonsense codon, TGA, or the four-base codon, AGGA, limiting us to a 21 amino acid code. To overcome this limitation, we have adapted a leucyl-tRNA synthetase from Methanobacterium thermoautotrophicum and leucyl tRNA derived from Halobacterium sp. NRC-1 as an orthogonal tRNA-synthetase pair in Escherichia coli to decode amber (TAG), opal (TGA), and four-base (AGGA) codons. To improve the efficiency and selectivity of the suppressor tRNA, extensive mutagenesis was performed on the anticodon loop and acceptor stem. The two most significant criteria required for an efficient amber orthogonal suppressor tRNA are a CU(X)XXXAA anticodon loop and the lack of noncanonical or mismatched base pairs in the stem regions. These changes afford only weak suppression of TGA and AGGA. However, this information together with an analysis of sequence similarity of multiple native archaeal tRNA sequences led to efficient, orthogonal suppressors of opal codons and the four-base codon, AGGA. Ultimately, it should be possible to use these additional orthogonal pairs to genetically incorporate multiple unnatural amino acids into proteins.
Anticodon↗
Structural dynamics of ribosomal RNA during decoding on the ribosome.
Decoding is a multistep process by which the ribosome accurately selects aminoacyl-tRNA (aa-tRNA) that matches the mRNA codon in the A site. The correct geometry of the codon-anticodon complex is monitored by the ribosome, resulting in conformational changes in the decoding center of the small (30S) ribosomal subunit by an induced-fit mechanism. The recognition of aa-tRNA is modulated by changes of the ribosome conformation in regions other than the decoding center that may either affect the architecture of the latter or alter the communication of the 30S subunit with the large (50S) subunit where the GTPase and peptidyl transferase centers are located. Correct codon-anticodon complex formation greatly accelerates the rates of GTP hydrolysis and peptide bond formation, indicating the importance of crosstalk between the subunits and the role of the 50S subunit in aa-tRNA selection. In the present review, recent results of the ribosome crystallography, cryoelectron microscopy (cryo-EM), genetics, rapid kinetics and biochemical approaches are reviewed which show that the dynamics of the structure of ribosomal RNA (rRNA) play a crucial role in decoding.
Anticodon↗
An asymmetric underlying rule in the assignment of codons: possible clue to a quick early evolution of the genetic code via successive binary choices.
Aminoacyl-tRNA synthetases (aaRSs) are responsible for creating the pool of correctly charged aminoacyl-tRNAs that are necessary for the translation of genetic information (mRNA) by the ribosome. Each aaRS belongs to either one of only two classes with two different mechanisms of aminoacylation, making use of either the 2'OH (Class I) or the 3'OH (Class II) of the terminal A76 of the tRNA and approaching the tRNA either from the minor groove (2'OH) or the major groove (3'OH). Here, an asymmetric pattern typical of differentiation is uncovered in the partition of the codon repertoire, as defined by the mechanism of aminoacylation of each corresponding tRNA. This pattern can be reproduced in a unique cascade of successive binary decisions that progressively reduces codon ambiguity. The deduced order of differentiation is manifestly driven by the reduction of translation errors. A simple rule can be defined, decoding each codon sequence in its binary class, thereby providing both the code and the key to decode it. Assuming that the partition into two mechanisms of tRNA aminoacylation is a relic that dates back to the invention of the genetic code in the RNA World, a model for the assignment of amino acids in the codon table can be derived. The model implies that the stop codon was always there, as the codon whose tRNA cannot be charged with any amino acid, and makes the prediction of an ultimate differentiation step, which is found to correspond to the codon assignment of the 22nd amino acid pyrrolysine in archaebacteria.
Amino Acyl-tRNA Synthetases↗