Dataset Information

Revisiting the Closed-Loop Model and the Nature of mRNA 5'-3' Communication.

ABSTRACT: Communication between the 5' and 3' ends of mature eukaryotic mRNAs lies at the heart of gene regulation, likely arising at the same time as the eukaryotic lineage itself. Our view of how and why it occurs has been shaped by elegant experiments that led to nearly universal acceptance of the "closed-loop model." However, new observations suggest that this classic model needs to be reexamined, revised, and expanded. Here, we address fundamental questions about the closed-loop model and discuss how a growing understanding of mRNA structure, dynamics, and intermolecular interactions presents new experimental opportunities. We anticipate that the application of emerging methods will lead to expanded models that include the role of intrinsic mRNA structure and quantitative dynamic descriptions of 5'-3' proximity linked to the functional status of an mRNA and will better reflect the messy realities of the crowded and rapidly changing cellular environment.

SUBMITTER: Vicens Q

PROVIDER: S-EPMC6294470 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Revisiting the Closed-Loop Model and the Nature of mRNA 5'-3' Communication.

Vicens Quentin Q Kieft Jeffrey S JS Rissland Olivia S OS

Molecular cell 20181201 5

Communication between the 5' and 3' ends of mature eukaryotic mRNAs lies at the heart of gene regulation, likely arising at the same time as the eukaryotic lineage itself. Our view of how and why it occurs has been shaped by elegant experiments that led to nearly universal acceptance of the "closed-loop model." However, new observations suggest that this classic model needs to be reexamined, revised, and expanded. Here, we address fundamental questions about the closed-loop model and discuss how ...[more]

PMID: 30526871

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Project description:Cardiac mechanical activity leads to periodic changes in the distribution of blood throughout the body, which causes micro-oscillations of the body's center of mass and can be measured by ballistocardiography (BCG). However, many of the BCG findings are based on parameters whose origins are poorly understood. Here, we generate simulated multidimensional BCG signals based on a more exhaustive and accurate computational model of blood circulation than previous attempts. This model consists in a closed loop 0D-1D multiscale representation of the human blood circulation. The 0D elements include the cardiac chambers, cardiac valves, arterioles, capillaries, venules, and veins, while the 1D elements include 55 systemic and 57 pulmonary arteries. The simulated multidimensional BCG signal is computed based on the distribution of blood in the different compartments and their anatomical position given by whole-body magnetic resonance angiography on a healthy young subject. We use this model to analyze the elements affecting the BCG signal on its different axes, allowing a better interpretation of clinical records. We also evaluate the impact of filtering and healthy aging on the BCG signal. The results offer a better view of the physiological meaning of BCG, as compared to previous models considering mainly the contribution of the aorta and focusing on longitudinal acceleration BCG. The shape of experimental BCG signals can be reproduced, and their amplitudes are in the range of experimental records. The contributions of the cardiac chambers and the pulmonary circulation are non-negligible, especially on the lateral and transversal components of the velocity BCG signal. The shapes and amplitudes of the BCG waveforms are changing with age, and we propose a scaling law to estimate the pulse wave velocity based on the time intervals between the peaks of the acceleration BCG signal. We also suggest new formulas to estimate the stroke volume and its changes based on the BCG signal expressed in terms of acceleration and kinetic energy.

Dataset Information

Revisiting the Closed-Loop Model and the Nature of mRNA 5'-3' Communication.

Publications

Revisiting the Closed-Loop Model and the Nature of mRNA 5'-3' Communication.

Similar Datasets

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