Infection by viruses, including herpes simplex virus-1 (HSV-1), and cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) in host genes. ...However, the underlying mechanisms remain unclear. Here, we demonstrate that the HSV-1 immediate early protein ICP27 induces DoTT by directly binding to the essential mRNA 3' processing factor CPSF. It thereby induces the assembly of a dead-end 3' processing complex, blocking mRNA 3' cleavage. Remarkably, ICP27 also acts as a sequence-dependent activator of mRNA 3' processing for viral and a subset of host transcripts. Our results unravel a bimodal activity of ICP27 that plays a key role in HSV-1-induced host shutoff and identify CPSF as an important factor that mediates regulation of transcription termination. These findings have broad implications for understanding the regulation of transcription termination by other viruses, cellular stress and cancer.
Alternative mRNA processing is a critical mechanism for proteome expansion and gene regulation in higher eukaryotes. The SR family proteins play important roles in splicing regulation. Intriguingly, ...mammalian genomes encode many poorly characterized SR-like proteins, including subunits of the mRNA 3′-processing factor CFIm, CFIm68 and CFIm59. Here we demonstrate that CFIm functions as an enhancer-dependent activator of mRNA 3′ processing. CFIm regulates global alternative polyadenylation (APA) by specifically binding and activating enhancer-containing poly(A) sites (PASs). Importantly, the CFIm activator functions are mediated by the arginine-serine repeat (RS) domains of CFIm68/59, which bind specifically to an RS-like region in the CPSF subunit Fip1, and this interaction is inhibited by CFIm68/59 hyper-phosphorylation. The remarkable functional similarities between CFIm and SR proteins suggest that interactions between RS-like domains in regulatory and core factors may provide a common activation mechanism for mRNA 3′ processing, splicing, and potentially other steps in RNA metabolism.
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•UGUA is a position-dependent enhancer for mRNA 3′ processing•CFIm is an enhancer-dependent activator of mRNA 3′ processing•The activator function of CFIm is mediated by its RS-like domains•mRNA 3′ processing and splicing share a common activation mechanism
Zhu et al. show that CFIm is an enhancer-dependent activator that promotes mRNA 3′-processing complex assembly. CFIm activator function requires the RS-like domains of CFIm68/59, and it involves a mechanism similar to SR protein-mediated splicing regulation, suggesting a unified activation mechanism for mRNA 3′ processing and splicing.
In response to the problem that the motor shaft of conventional tubular linear motor is prone to bending, this paper proposes a new tubular linear motor structure for large thrust demand. Bending of ...the motor shaft can lead to collisions between structures and affect motor performance, and traditional air-gap structures cannot effectively handle this problem. The stator of the new motor is divided into an inner and outer cylinder structure. The armature windings are arranged between the inner and outer cylinders. The permanent magnets are arranged on the motor shaft. After analysis, the structural proposed in this paper can well stop the bending of the motor shaft. It also effectively improves the problem of large fluctuations in the thrust of linear motors. Finally, it is concluded that the peak motor thrust is maximized when the material with low permeability is chosen for the inner cylinder.
Cell fate transitions involve rapid gene expression changes and global chromatin remodeling, yet the underlying regulatory pathways remain incompletely understood. Here, we identified the ...RNA-processing factor Nudt21 as a novel regulator of cell fate change using transcription-factor-induced reprogramming as a screening assay. Suppression of Nudt21 enhanced the generation of induced pluripotent stem cells, facilitated transdifferentiation into trophoblast stem cells, and impaired differentiation of myeloid precursors and embryonic stem cells, suggesting a broader role for Nudt21 in cell fate change. We show that Nudt21 directs differential polyadenylation of over 1,500 transcripts in cells acquiring pluripotency, although only a fraction changed protein levels. Remarkably, these proteins were strongly enriched for chromatin regulators, and their suppression neutralized the effect of Nudt21 during reprogramming. Collectively, our data uncover Nudt21 as a novel post-transcriptional regulator of cell fate and establish a direct, previously unappreciated link between alternative polyadenylation and chromatin signaling.
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•shRNA screen identifies mRNA processing factor Nudt21 as a regulator of cell fate•Nudt21 knockdown enhances reprogramming but disrupts ESC/myeloid differentiation•Nudt21 suppression induces alternative polyadenylation for hundreds of transcripts•Chromatin regulators are enriched among Nudt21 targets important for reprogramming
Alternative polyadenylation exerts post-transcriptional control over cell fate decisions and pluripotency.
We consider an uncertain mechanical system. The uncertainty includes the initial condition and system parameter. The uncertain parameter in the system is (possibly fast) time varying. The only known ...information about the uncertainty is that it lies in a fuzzy set. The mechanical system is to follow a set of constraints, which may include many engineering applications, even in the presence of uncertainty. For this purpose, we propose a β-measure for constraint obedience, which reflects how much this constraint is obeyed. Based on a very general Lyapunov function, a control scheme is proposed to render a twofold performance: guaranteed and optimal. In the guaranteed phase, the β-measure is assured to be uniformly bounded and uniformly ultimately bounded, regardless of the actual value of the uncertainty. In the optimal phase, a fuzzy-theoretic-based performance, by which both the "average" β-measure and control effort are considered, is minimized. As a result, the control serves the practical engineering purposes: The mechanical system is guaranteed to follow the desired task with the minimum cost. This paper is part of a unique endeavor to cast both the descriptions of the uncertainty and desired performance index into a fuzzy framework.
A tracking stability control problem for the vertical electric stabilization system of moving tank based on adaptive robust servo control is addressed. This paper mainly focuses on two types of ...possibly fast time-varying but bounded uncertainty within the vertical electric stabilization system: model parameter uncertainty and uncertain nonlinearity. First, the vertical electric stabilization system is constructed as an uncertain nonlinear dynamic system that can reflect the practical mechanics transfer process of the system. Second, the dynamical equation in the form of state space is established by designing the angular tracking error. Third, the comprehensive parameter of system uncertainty is designed to estimate the most conservative effects of uncertainty. Finally, an adaptive robust servo control which can effectively handle the combined effects of complex nonlinearity and uncertainty is proposed. The feasibility of the proposed control strategy under the practical physical condition is validated through the tests on the experimental platform. This paper pioneers the introduction of the internal nonlinearity and uncertainty of the vertical electric stabilization system into the settlement of the tracking stability control problem, and validates the advanced servo control strategy through experiment for the first time.
This paper focuses on the problem of target tracking control of marching tanks under the condition of high-speed maneuver based on sliding mode disturbance observer. First, the dynamic model of ...marching tank is established by using multi-body dynamics software. The nonlinear factors such as barrel flexibility, clearance between barrel and bushing, and uncertainty sources such as road excitation are considered. Second, the mechatronics model of tank bidirectional stabilization system considering transmission clearance and friction is established in numerical simulation software. Aiming at the tank bidirectional stabilization system, an adaptive robust controller based on sliding mode disturbance observer is designed. Finally, the real-time control and target tracking of the tank bidirectional stabilization system are realized by co-simulation. The results show that the sliding mode disturbance observer improves the stability accuracy of the system by 43.22 %. Comparing the simulation results with the PID control, the controller designed in this paper has the characteristics of rapid tracking speed and high robustness, and the advantage is more obvious under the condition of high-speed maneuver.
This paper proposes a cooperative game-oriented optimal design problem of robust control for uncertain mechanical systems. State of the concerned system is affected by (possibly fast) time-varying ...but bounded uncertainty. The task is to drive the system to obey a set of prescribed constraints. A
β
-measure is defined to gauge the constraint-following error; based on which, a robust control with two tunable parameters is then proposed to render the system to be uniform boundedness and uniform ultimate boundedness. For the seeking of the optimal design parameters, two cost functions, each of which is dominated by one tunable parameter, are developed, and thereout a two-player cooperative game is formulated. Finally, the optimal design problem is successfully solved: with the
existence
,
uniqueness
, and
analytical expression
of the Pareto-optimality. This paper is the first ever endeavor to cast both constraint following and cooperative game into control framework for uncertain mechanical systems.
Stability control of the tank gun has emerged as a pivotal issue for moving tank gun control systems (TGCS). As a complex electromechanical integrated system, TGCS of moving tank inevitably possesses ...significant parametric uncertainties and uncertain nonlinearities. To effectively enhance the stabilization control performance of TGCS, in this study, we introduce an adaptive robust control (ARC) strategy based on radial basis function neural network (RBFNN) compensation. The adaptive technique is employed to address the parametric uncertainties, while the RBFNN is constructed to approximate the uncertain nonlinearities and realize feedforward compensation. Subsequently, to suppress the residual uncertainties, a nonlinear robust feedback control rate is devised to strengthen the robustness of the developed controller. Lyapunov analysis shows that the proposed controller achieves uniform ultimate bounded stability. Extensive simulation and electromechanical experimental results confirm the effectiveness of the proposed controller, which shows outstanding performance in handling strong parametric uncertainties and uncertain nonlinearities.
This article proposes a robust control optimization design problem based on Nash game-theoretic for the marching tank bi-directional stabilization system of an all-electric actuator, which is ...accompanied by complex uncertainty (possibly fast time-varying but bounded). The task is to drive the barrel firing angle to adjust to a specified position under complex uncertainty while ensuring that multiple design parameters are optimally chosen in the controller. Firstly, the machine-electric coupled dynamics equations with uncertainty are created in the form of state space. Secondly, a robust controller with two design parameters to be chosen is given so that the constraint following error has uniform boundedness and uniform ultimate boundedness. Thirdly, a Nash game cost function consisting of three components: performance cost, time cost and control cost is proposed, and the Nash equilibrium (i.e., optimal control parameters) is obtained by minimizing the cost function. Finally, a co-simulation experimental platform is built to verify the robustness of the controller under complex uncertainty (modeling errors, uncertain disturbances and road excitation) and to demonstrate the global optimal performance of the system under optimal design parameters.
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