The temperature dependence of amino acid hydrophobicity data is related to the genetic coding algorithm for complementary (sense and antisense) peptide interactions.
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ABSTRACT:
SUBMITTER: Stambuk N
PROVIDER: S-EPMC7138962 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The hydrophobicities of the 20 common amino acids are reflected in their tendencies to appear in interior positions in globular proteins and in deeply buried positions of membrane proteins. To determine whether these relationships might also have been valid in the warm surroundings where life may have originated, we examined the effect of temperature on the hydrophobicities of the amino acids as measured by the equilibrium constants for transfer of their side-chains from neutral solution to cyclohexane (K(w > c)). The hydrophobicities of most amino acids were found to increase with increasing temperature. Because that effect is more pronounced for the more polar amino acids, the numerical range of K(w > c) values decreases with increasing temperature. There are also modest changes in the ordering of the more polar amino acids. However, those changes are such that they would have tended to minimize the otherwise disruptive effects of a changing thermal environment on the evolution of protein structure. Earlier, the genetic code was found to be organized in such a way that--with a single exception (threonine)--the side-chain dichotomy polar/nonpolar matches the nucleic acid base dichotomy purine/pyrimidine at the second position of each coding triplet at 25 °C. That dichotomy is preserved at 100 °C. The accessible surface areas of amino acid side-chains in folded proteins are moderately correlated with hydrophobicity, but when free energies of vapor-to-cyclohexane transfer (corresponding to size) are taken into consideration, a closer relationship becomes apparent.
| S-EPMC4475965 | biostudies-literature
Project description:BackgroundThere is increasing realization that regulation of genes is done partly at the RNA level by sense-antisense binding. Studies typically concentrate on the role of non-coding RNAs in regulating coding RNA. But the majority of transcripts in a cell are likely to be coding. Is it possible that coding RNA might regulate other coding RNA by short perfect sense-antisense binding? Here we compare all well-described human protein coding mRNAs against all others to identify sites 15-25 bp long that could potentially perfectly match sense-antisense.ResultsFrom 24,968 protein coding mRNA RefSeq sequences, none failed to find at least one match in the transcriptome. By randomizations generating artificial transcripts matched for G+C content and length, we found that there are more such trans short sense-antisense pairs than expected. Several further features are consistent with functionality of some of the putative matches. First, transcripts with more potential partners have lower expression levels, and the pair density of tissue specific genes is significantly higher than that of housekeeping genes. Further, the single nucleotide polymorphism density is lower in short pairing regions than it is in flanking regions. We found no evidence that the sense-antisense pairing regions are associated with small RNAs derived from the protein coding genes.ConclusionsOur results are consistent with the possibility of common short perfect sense-antisense pairing between transcripts of protein coding genes.
| S-EPMC2646273 | biostudies-literature
Project description:Several transient receptor potential (TRP) ion channels can be directly activated by hot or cold temperature with high sensitivity. However, the structures and molecular mechanism giving rise to their high temperature sensitivity are not fully understood. One hypothesized mechanism assumes that temperature activation is driven by the exposure of hydrophobic residues to solvent. This mechanism further predicts that residues are exposed to solvent in a coordinated fashion, but without necessarily being located in close proximity to each other. However, there is little experimental evidence supporting this mechanism in TRP channels. Here, we combined high-throughput mutagenesis, functional screening, and deep sequencing to identify mutations from a total of ~7,300 TRPV1 random mutant clones. We found that strong decreases in hydrophobicity of amino acids are better tolerated for activation by capsaicin than for activation by hot temperature, suggesting that strong hydrophobicity might be specifically required for temperature activation. Altogether, our work provides initial correlative support for a previously hypothesized temperature mechanism in TRP ion channels.
| S-EPMC5428820 | biostudies-literature
Project description:BACKGROUND: Alus are primate-specific retrotransposons which account for 10.6% of the human genome. A large number of protein-coding mRNAs are encoded with sense or antisense Alus in the un-translated regions. RESULTS: We postulated that mRNAs carrying Alus in the two opposite directions can generate double stranded RNAs, capable of regulating the levels of other Alu-carrying mRNAs post-transcriptionally. A gene expression profiling assay showed that the levels of antisense and sense Alus-carrying mRNAs were suppressed in a reversible manner by over-expression of exogenous sense and antisense Alus derived from mRNAs (Family-wise error rate P=0.0483 and P<0.0001 respectively). Screening through human mRNAs on the NCBI-RefSeq database, it was found that sense and antisense Alu-carrying transcripts were enriched in distinct cellular functions. Antisense Alu-carrying genes were particularly enriched in neurological and developmental processes, while sense Alu-carrying genes were enriched in immunological functions. CONCLUSIONS: Taken together, we proposed a novel Alu-mediated regulation network capable of stabilizing Alu-carrying mRNA levels in different cell types and restricting the activated expression levels of protein-coding, Alu-carrying mRNAs.
| S-EPMC3655826 | biostudies-literature
Project description:The genetic basis for most inherited neurodegenerative diseases has been identified, yet there are limited disease-modifying therapies for these patients. A new class of drugs-antisense oligonucleotides (ASOs)-show promise as a therapeutic platform for treating neurological diseases. ASOs are designed to bind to the RNAs either by promoting degradation of the targeted RNA or by elevating expression by RNA splicing. Intrathecal injection into the cerebral spinal fluid results in broad distribution of antisense drugs and long-term effects. Approval of nusinersen in 2016 demonstrated that effective treatments for neurodegenerative diseases can be identified and that treatments not only slow disease progression but also improve some symptoms. Antisense drugs are currently in development for amyotrophic lateral sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, and Angelman syndrome, and several drugs are in late-stage research for additional neurological diseases. This review highlights the advances in antisense technology as potential treatments for neurological diseases.
| S-EPMC8682074 | biostudies-literature
Project description:The hydrophobic effect is the main driving force in protein folding. One can estimate the relative strength of this hydrophobic effect for each amino acid by mining a large set of experimentally determined protein structures. However, the hydrophobic force is known to be strongly temperature dependent. This temperature dependence is thought to explain the denaturation of proteins at low temperatures. Here we investigate if it is possible to extract this temperature dependence directly from a large set of protein structures determined at different temperatures. Using NMR structures filtered for sequence identity, we were able to extract hydrophobicity propensities for all amino acids at five different temperature ranges (spanning 265-340 K). These propensities show that the hydrophobicity becomes weaker at lower temperatures, in line with current theory. Alternatively, one can conclude that the temperature dependence of the hydrophobic effect has a measurable influence on protein structures. Moreover, this work provides a method for probing the individual temperature dependence of the different amino acid types, which is difficult to obtain by direct experiment.
| S-EPMC4441443 | biostudies-literature
Project description:We tested the idea that ancestral class I and II aminoacyl-tRNA synthetases arose on opposite strands of the same gene. We assembled excerpted 94-residue Urgenes for class I tryptophanyl-tRNA synthetase (TrpRS) and class II Histidyl-tRNA synthetase (HisRS) from a diverse group of species, by identifying and catenating three blocks coding for secondary structures that position the most highly conserved, active-site residues. The codon middle-base pairing frequency was 0.35 ± 0.0002 in all-by-all sense/antisense alignments for 211 TrpRS and 207 HisRS sequences, compared with frequencies between 0.22 ± 0.0009 and 0.27 ± 0.0005 for eight different representations of the null hypothesis. Clustering algorithms demonstrate further that profiles of middle-base pairing in the synthetase antisense alignments are correlated along the sequences from one species-pair to another, whereas this is not the case for similar operations on sets representing the null hypothesis. Most probable reconstructed sequences for ancestral nodes of maximum likelihood trees show that middle-base pairing frequency increases to approximately 0.42 ± 0.002 as bacterial trees approach their roots; ancestral nodes from trees including archaeal sequences show a less pronounced increase. Thus, contemporary and reconstructed sequences all validate important bioinformatic predictions based on descent from opposite strands of the same ancestral gene. They further provide novel evidence for the hypothesis that bacteria lie closer than archaea to the origin of translation. Moreover, the inverse polarity of genetic coding, together with a priori α-helix propensities suggest that in-frame coding on opposite strands leads to similar secondary structures with opposite polarity, as observed in TrpRS and HisRS crystal structures.
| S-EPMC3684856 | biostudies-literature
Project description:OBJECTIVE:To identify differentially expressed long non-coding RNA (lncRNA) genes in human myometrium in women with spontaneous labor at term. MATERIALS AND METHODS:Myometrium was obtained from women undergoing cesarean deliveries who were not in labor (n = 19) and women in spontaneous labor at term (n = 20). RNA was extracted and profiled using an Illumina® microarray platform. We have used computational approaches to bound the extent of long non-coding RNA representation on this platform, and to identify co-differentially expressed and correlated pairs of long non-coding RNA genes and protein-coding genes sharing the same genomic loci. RESULTS:We identified co-differential expression and correlation at two genomic loci that contain coding-lncRNA gene pairs: SOCS2-AK054607 and LMCD1-NR_024065 in women in spontaneous labor at term. This co-differential expression and correlation was validated by qRT-PCR, an experimental method completely independent of the microarray analysis. Intriguingly, one of the two lncRNA genes differentially expressed in term labor had a key genomic structure element, a splice site, that lacked evolutionary conservation beyond primates. CONCLUSIONS:We provide, for the first time, evidence for coordinated differential expression and correlation of cis-encoded antisense lncRNAs and protein-coding genes with known as well as novel roles in pregnancy in the myometrium of women in spontaneous labor at term.
| S-EPMC4208830 | biostudies-literature
Project description:Understanding and quantifying the temperature dependence of population parameters, such as intrinsic growth rate and carrying capacity, is critical for predicting the ecological responses to environmental change. Many studies provide empirical estimates of such temperature dependencies, but a thorough investigation of the methods used to infer them has not been performed yet. We created artificial population time series using a stochastic logistic model parameterized with the Arrhenius equation, so that activation energy drives the temperature dependence of population parameters. We simulated different experimental designs and used different inference methods, varying the likelihood functions and other aspects of the parameter estimation methods. Finally, we applied the best performing inference methods to real data for the species Paramecium caudatum. The relative error of the estimates of activation energy varied between 5% and 30%. The fraction of habitat sampled played the most important role in determining the relative error; sampling at least 1% of the habitat kept it below 50%. We found that methods that simultaneously use all time series data (direct methods) and methods that estimate population parameters separately for each temperature (indirect methods) are complementary. Indirect methods provide a clearer insight into the shape of the functional form describing the temperature dependence of population parameters; direct methods enable a more accurate estimation of the parameters of such functional forms. Using both methods, we found that growth rate and carrying capacity of Paramecium caudatum scale with temperature according to different activation energies. Our study shows how careful choice of experimental design and inference methods can increase the accuracy of the inferred relationships between temperature and population parameters. The comparison of estimation methods provided here can increase the accuracy of model predictions, with important implications in understanding and predicting the effects of temperature on the dynamics of populations.
| S-EPMC4278823 | biostudies-literature
Project description:We have designed a heterofunctionalized nanoparticle conjugate consisting of a 13-nm gold nanoparticle (Au NP) containing both antisense oligonucleotides and synthetic peptides. The synthesis of this conjugate is accomplished by mixing thiolated oligonucleotides and cysteine-terminated peptides with gold nanoparticles in the presence of salt, which screens interactions between biomolecules, yielding a densely functionalized nanomaterial. By controlling the stoichiometry of the components in solution, we can control the surface loading of each biomolecule. The conjugates are prepared easily and show perinuclear localization and an enhanced gene regulation activity when tested in a cellular model. This heterofunctionalized structure represents a new strategy for preparing nanomaterials with potential therapeutic applications.
| S-EPMC2582275 | biostudies-literature