Heterogeneous recruitment abilities to RNA polymerases generate nonlinear scaling of gene expression with cell volume.
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ABSTRACT:
SUBMITTER: Wang Q
PROVIDER: S-EPMC8617254 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCellular RNA polymerases are highly conserved enzymes that undergo complex conformational changes to coordinate the processing of nucleic acid substrates through the active site. Two domains in particular, the bridge helix and the trigger loop, play a key role in this mechanism by adopting different conformations at various stages of the nucleotide addition cycle. The functional relevance of these structural changes has been difficult to assess from the relatively small number of static crystal structures currently available.ResultsUsing a novel robotic approach we characterized the functional properties of 367 site-directed mutants of the Methanocaldococcus jannaschii RNA polymerase A' subunit, revealing a wide spectrum of in vitro phenotypes. We show that a surprisingly large number of single amino acid substitutions in the bridge helix, including a kink-inducing proline substitution, increase the specific activity of RNA polymerase. Other 'superactivating' substitutions are located in the adjacent base helices of the trigger loop.ConclusionThe results support the hypothesis that the nucleotide addition cycle involves a kinked bridge helix conformation. The active center of RNA polymerase seems to be constrained by a network of functional interactions between the bridge helix and trigger loop that controls fundamental parameters of RNA synthesis.
| S-EPMC2776397 | biostudies-literature
Project description:RNA polymerase II (Pol II) small nuclear RNA (snRNA) promoters and type 3 Pol III promoters have highly similar structures; both contain an interchangeable enhancer and "proximal sequence element" (PSE), which recruits the SNAP complex (SNAPc). The main distinguishing feature is the presence, in the type 3 promoters only, of a TATA box, which determines Pol III specificity. To understand the mechanism by which the absence or presence of a TATA box results in specific Pol recruitment, we examined how SNAPc and general transcription factors required for Pol II or Pol III transcription of SNAPc-dependent genes (i.e., TATA-box-binding protein [TBP], TFIIB, and TFIIA for Pol II transcription and TBP and BRF2 for Pol III transcription) assemble to ensure specific Pol recruitment. TFIIB and BRF2 could each, in a mutually exclusive fashion, be recruited to SNAPc. In contrast, TBP-TFIIB and TBP-BRF2 complexes were not recruited unless a TATA box was present, which allowed selective and efficient recruitment of the TBP-BRF2 complex. Thus, TBP both prevented BRF2 recruitment to Pol II promoters and enhanced BRF2 recruitment to Pol III promoters. On Pol II promoters, TBP recruitment was separate from TFIIB recruitment and enhanced by TFIIA. Our results provide a model for specific Pol recruitment at SNAPc-dependent promoters.
| S-EPMC6004067 | biostudies-literature
Project description:The Poisson equation is a widely accepted model for electrostatic analysis. However, the Poisson equation is derived based on electric polarizations in a linear, isotropic, and homogeneous dielectric medium. This article introduces a nonlinear Poisson equation to take into consideration of hyperpolarization effects due to intensive charges and possible nonlinear, anisotropic, and heterogeneous media. Variational principle is utilized to derive the nonlinear Poisson model from an electrostatic energy functional. To apply the proposed nonlinear Poisson equation for the solvation analysis, we also construct a nonpolar solvation energy functional based on the nonlinear Poisson equation by using the geometric measure theory. At a fixed temperature, the proposed nonlinear Poisson theory is extensively validated by the electrostatic analysis of the Kirkwood model and a set of 20 proteins, and the solvation analysis of a set of 17 small molecules whose experimental measurements are also available for a comparison. Moreover, the nonlinear Poisson equation is further applied to the solvation analysis of 21 compounds at different temperatures. Numerical results are compared to theoretical prediction, experimental measurements, and those obtained from other theoretical methods in the literature. A good agreement between our results and experimental data as well as theoretical results suggests that the proposed nonlinear Poisson model is a potentially useful model for electrostatic analysis involving hyperpolarization effects.
| S-EPMC3443777 | biostudies-literature
Project description:We present a statistical analysis of music scores from different composers using detrended fluctuation analysis (DFA). We find different fluctuation profiles that correspond to distinct autocorrelation structures of the musical pieces. Further, we reveal evidence for the presence of nonlinear autocorrelations by estimating the DFA of the magnitude series, a result validated by a corresponding study of appropriate surrogate data. The amount and the character of nonlinear correlations vary from one composer to another. Finally, we performed a simple experiment in order to evaluate the pleasantness of the musical surrogate pieces in comparison with the original music and find that nonlinear correlations could play an important role in the aesthetic perception of a musical piece.
| S-EPMC5750023 | biostudies-literature
Project description:Update rules, which describe how individuals adjust their behavior over time, affect the outcome of social interactions. Theoretical studies have shown that evolutionary outcomes are sensitive to model details when update rules are imitation-based but are robust when update rules are self-evaluation based. However, studies of self-evaluation based rules have focused on homogeneous population structures where each individual has the same number of neighbors. Here, we consider heterogeneous population structures represented by weighted networks. Under weak selection, we analytically derive the condition for strategy success, which coincides with the classical condition of risk-dominance. This condition holds for all weighted networks and distributions of aspiration levels, and for individualized ways of self-evaluation. Our findings recover previous results as special cases and demonstrate the universality of the robustness property under self-evaluation based rules. Our work thus sheds light on the intrinsic difference between evolutionary dynamics under self-evaluation based and imitation-based update rules.
| S-EPMC8166829 | biostudies-literature
Project description:For cellular structures with uniform geometry, cell size and distribution, made from a neo-Hookean material, we demonstrate experimentally that large stretching causes nonlinear scaling effects governed by the microstructural architecture and the large strains at the cell level, which are not predicted by the linear elastic theory. For this purpose, three honeycomb-like structures with uniform square cells in stacked distribution were designed, where the number of cells varied, while the material volume and the ratio between the thickness and the length of the cell walls were fixed. These structures were manufactured from silicone rubber and tested under large uniaxial tension in a bespoke test fixture. Optical strain measurements were used to assess the deformation by capturing both the global displacements of the structure and the local deformations in the form of a strain map. The experimental results showed that, under sufficiently large strains, there was an increase in the stiffness of the structure when the same volume of material was arranged as many small cells compared to when it was organized as fewer larger cells. Finite element simulations confirmed our experimental findings. This study sheds light upon the nonlinear elastic responses of cellular structures in large-strain deformations, which cannot be captured within the linear elasticity framework.
| S-EPMC6366230 | biostudies-literature
Project description:The flight ability of animals is restricted by the scaling effects imposed by physical and physiological factors. In comparisons of the power available from muscle and the mechanical power required to fly, it is predicted that the margin between the powers should decrease with body size and that flying animals have a maximum body size. However, predicting the absolute value of this upper limit has proven difficult because wing morphology and flight styles varies among species. Albatrosses and petrels have long, narrow, aerodynamically efficient wings and are considered soaring birds. Here, using animal-borne accelerometers, we show that soaring seabirds have two modes of flapping frequencies under natural conditions: vigorous flapping during takeoff and sporadic flapping during cruising flight. In these species, high and low flapping frequencies were found to scale with body mass (mass(-0.30) and mass(-0.18)) in a manner similar to the predictions from biomechanical flight models (mass(-1/3) and mass(-1/6)). These scaling relationships predicted that the maximum limits on the body size of soaring animals are a body mass of 41 kg and a wingspan of 5.1 m. Albatross-like animals larger than the limit will not be able to flap fast enough to stay aloft under unfavourable wind conditions. Our result therefore casts doubt on the flying ability of large, extinct pterosaurs. The largest extant soarer, the wandering albatross, weighs about 12 kg, which might be a pragmatic limit to maintain a safety margin for sustainable flight and to survive in a variable environment.
| S-EPMC2670537 | biostudies-literature
Project description:BackgroundVoice disorders affect patients profoundly, and acoustic tools can potentially measure voice function objectively. Disordered sustained vowels exhibit wide-ranging phenomena, from nearly periodic to highly complex, aperiodic vibrations, and increased "breathiness". Modelling and surrogate data studies have shown significant nonlinear and non-Gaussian random properties in these sounds. Nonetheless, existing tools are limited to analysing voices displaying near periodicity, and do not account for this inherent biophysical nonlinearity and non-Gaussian randomness, often using linear signal processing methods insensitive to these properties. They do not directly measure the two main biophysical symptoms of disorder: complex nonlinear aperiodicity, and turbulent, aeroacoustic, non-Gaussian randomness. Often these tools cannot be applied to more severe disordered voices, limiting their clinical usefulness.MethodsThis paper introduces two new tools to speech analysis: recurrence and fractal scaling, which overcome the range limitations of existing tools by addressing directly these two symptoms of disorder, together reproducing a "hoarseness" diagram. A simple bootstrapped classifier then uses these two features to distinguish normal from disordered voices.ResultsOn a large database of subjects with a wide variety of voice disorders, these new techniques can distinguish normal from disordered cases, using quadratic discriminant analysis, to overall correct classification performance of 91.8 +/- 2.0%. The true positive classification performance is 95.4 +/- 3.2%, and the true negative performance is 91.5 +/- 2.3% (95% confidence). This is shown to outperform all combinations of the most popular classical tools.ConclusionGiven the very large number of arbitrary parameters and computational complexity of existing techniques, these new techniques are far simpler and yet achieve clinically useful classification performance using only a basic classification technique. They do so by exploiting the inherent nonlinearity and turbulent randomness in disordered voice signals. They are widely applicable to the whole range of disordered voice phenomena by design. These new measures could therefore be used for a variety of practical clinical purposes.
| S-EPMC1913514 | biostudies-literature
Project description:RNA-dependent RNA polymerases (RdRPs) play key roles in viral transcription and genome replication, as well as epigenetic and post-transcriptional control of cellular gene expression. In this article, we review the crystallographic, biochemical, and molecular genetic data available for viral RdRPs that have led to a detailed description of substrate and cofactor binding, fidelity of nucleotide selection and incorporation, and catalysis. It is likely that the cellular RdRPs will share some of the basic structural and mechanistic principles gleaned from studies of viral RdRPs. Therefore, studies of the viral RdRP establish a framework for the study of cellular RdRPs, an important yet understudied class of nucleic acid polymerases.
| S-EPMC2441838 | biostudies-literature
Project description:In both humans and mice, the efficacy of working memory capacity and its related process, selective attention, are each strongly predictive of individuals' aggregate performance in cognitive test batteries [1-9]. Because working memory is taxed during most cognitive tasks, the efficacy of working memory may have a causal influence on individuals' performance on tests of "intelligence" [10, 11]. Despite the attention this has received, supporting evidence has been largely correlational in nature (but see [12]). Here, genetically heterogeneous mice were assessed on a battery of five learning tasks. Animals' aggregate performance across the tasks was used to estimate their general cognitive abilities, a trait that is in some respects analogous to intelligence [13, 14]. Working memory training promoted an increase in animals' selective attention and their aggregate performance on these tasks. This enhancement of general cognitive performance by working memory training was attenuated if its selective attention demands were reduced. These results provide evidence that the efficacy of working memory capacity and selective attention may be causally related to an animal's general cognitive performance and provide a framework for behavioral strategies to promote those abilities. Furthermore, the pattern of behavior reported here reflects a conservation of the processes that regulate general cognitive performance in humans and infrahuman animals.
| S-EPMC2910164 | biostudies-literature