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Free, publicly-accessible full text available June 12, 2025
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Finley, Stacey D (Ed.)
In experiments, the distributions of mRNA or protein numbers in single cells are often fitted to the random telegraph model which includes synthesis and decay of mRNA or protein, and switching of the gene between active and inactive states. While commonly used, this model does not describe how fluctuations are influenced by crucial biological mechanisms such as feedback regulation, non-exponential gene inactivation durations, and multiple gene activation pathways. Here we investigate the dynamical properties of four relatively complex gene expression models by fitting their steady-state mRNA or protein number distributions to the simple telegraph model. We show that despite the underlying complex biological mechanisms, the telegraph model with three effective parameters can accurately capture the steady-state gene product distributions, as well as the conditional distributions in the active gene state, of the complex models. Some effective parameters are reliable and can reflect realistic dynamic behaviors of the complex models, while others may deviate significantly from their real values in the complex models. The effective parameters can also be applied to characterize the capability for a complex model to exhibit multimodality. Using additional information such as single-cell data at multiple time points, we provide an effective method of distinguishing the complex models from the telegraph model. Furthermore, using measurements under varying experimental conditions, we show that fitting the mRNA or protein number distributions to the telegraph model may even reveal the underlying gene regulation mechanisms of the complex models. The effectiveness of these methods is confirmed by analysis of single-cell data for
E. coli and mammalian cells. All these results are robust with respect to cooperative transcriptional regulation and extrinsic noise. In particular, we find that faster relaxation speed to the steady state results in more precise parameter inference under large extrinsic noise.Free, publicly-accessible full text available May 14, 2025 -
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Abstract Background Morphological properties of tissues and organs rely on cell growth. The growth of plant cells is determined by properties of a tough outer cell wall that deforms anisotropically in response to high turgor pressure. Cortical microtubules bias the mechanical anisotropy of a cell wall by affecting the trajectories of cellulose synthases in the wall that polymerize cellulose microfibrils. The microtubule cytoskeleton is often oriented in one direction at cellular length-scales to regulate growth direction, but the means by which cellular-scale microtubule patterns emerge has not been well understood. Correlations between the microtubule orientation and tensile forces in the cell wall have often been observed. However, the plausibility of stress as a determining factor for microtubule patterning has not been directly evaluated to date.
Results Here, we simulated how different attributes of tensile forces in the cell wall can orient and pattern the microtubule array in the cortex. We implemented a discrete model with transient microtubule behaviors influenced by local mechanical stress in order to probe the mechanisms of stress-dependent patterning. Specifically, we varied the sensitivity of four types of dynamic behaviors observed on the plus end of microtubules – growth, shrinkage, catastrophe, and rescue – to local stress. Then, we evaluated the extent and rate of microtubule alignments in a two-dimensional computational domain that reflects the structural organization of the cortical array in plant cells.
Conclusion Our modeling approaches reproduced microtubule patterns observed in simple cell types and demonstrated that a spatial variation in the magnitude and anisotropy of stress can mediate mechanical feedback between the wall and of the cortical microtubule array.
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Abstract Alternative splicing (AS) significantly enriches the diversity of transcriptomes and proteomes, playing a pivotal role in the physiology and development of eukaryotic organisms. With the continuous advancement of high-throughput sequencing technologies, an increasing number of novel transcript isoforms, along with factors related to splicing and their associated functions, are being unveiled. In this review, we succinctly summarize and compare the different splicing mechanisms across prokaryotes and eukaryotes. Furthermore, we provide an extensive overview of the recent progress in various studies on AS covering different developmental stages in diverse plant species and in response to various abiotic stresses. Additionally, we discuss modern techniques for studying the functions and quantification of AS transcripts, as well as their protein products. By integrating genetic studies, quantitative methods, and high-throughput omics techniques, we can discover novel transcript isoforms and functional splicing factors, thereby enhancing our understanding of the roles of various splicing modes in different plant species.