Mechanical force regulates a variety of cellular functions through inducing modulations in nuclear chromatin structures and epigenetic landscapes (outside in). The epigenetic modifications, in turn, regulate gene expressions and affect phenotypic outcomes, including cytoskeletal organization and cell–cell/cell–ECM interactions (inside out). While there have been significant advances in the understanding of mechanotransduction in the nucleus, there is still a lack of knowledge on the potential mechanisms through which mechanical cues affect epigenetic and chromatin regulations to determine genetic outcomes. This review firstly focuses on the current understanding of epigenetic regulations and then summarizes how mechanotransduction and epigenetic modification couple together to regulate molecular and cellular functions, eventually causing functional phenotype changes e.g. , diseases. Lastly, we introduce related technologies for mechanistic studies, particularly fluorescence resonance energy transfer (FRET) biosensors for the visualization of dynamic epigenetic regulations in single living cells, as well as the applications of FRET biosensors to visualize mechanotransduction events occurring in the nucleus. These studies could provide new insights into epigenetics in regulating the physiological and pathological processes in living cells under different mechanical environments.
In eukaryotic cells,the endoplasmic reticulum (ER) forms a continuous network of tubules and sheets.ER membranes are inter-connected by a class of dynamin-like GTPases termed atlastins (ATLs).Deletion or mutation of ATLs results in long and unbranched ER tubules in cells.Mutations in ATL1 in humans have been linked to the neurodegenerative disease hereditary spastic paraplegia.The basis of ATL-mediated membrane fusion has been studied extensively,but specific functions of ATL remain unclear.In this review,we summarize ER-related cellular processes that directly or indirectly involve ATL,including membrane trafficking,lipid metabolism,autophagy,microtubule dynamics,pathogen infections,calcium signaling,and protein homeostasis.These findings provide important clues for deciphering the physiological roles of the tubular ER network.
Tubulin posttranslational modifications (PTMs) add "tubulin code" to generate functional diversities of microtubules.Several types of tubulin PTMs accumulate on axonemes and basal bodies of cilia,including acetylation,glutamylation,glycylation and detyrosination.Among them,glutamylation,glycylation and detyrosination are mostly enriched in the B-tubules,whereas acetylation occurs on both A-and B-tubule of the microtubule doublets in a similar level.Recent studies indicate that tubulin PTMs are critical for the fine tuning of assembly/disassembly,maintenance,motility,and signaling of cilia.Dysregulated tubulin PTMs are strongly implicated in human disorders including ciliopathies and neuron degeneration.Here,we review the current understanding how tubulin PTMs regulate cilia formation and function,and their relevance to human health.
Noncoding RNAs play important roles in cell and their secondary structures are vital for understanding their tertiary structures and functions.Many prediction methods of RNA secondary structures have been proposed but it is still challenging to reach high accuracy,especially for those with pseudoknots.Here we present a coupled deep learning model,called 2dRNA,to predict RNA secondary structure.It combines two famous neural network architectures bidirectional LSTM and U-net and only needs the sequence of a target RNA as input.Benchmark shows that our method can achieve state-of-the-art performance compared to current methods on a testing dataset.Our analysis also shows that 2dRNA can learn structural information from similar RNA sequences without aligning them.
Mechanical properties of brain tissue can provide vital information for understanding the mechanism of traumatic brain injury (TBI).As mouse models were commonly adopted for TBI studies,a method to produce injury to the brain and characterize the injured tissue is desired.In this paper,a complete workflow of TBI induction,sample preparation,and biomechanical characterization is presented for measurement of the injured brain tissue.A controlled cortical impact device was used to induce injury to the brain.By setting the angle,speed,and position of the impact,the level of brain injuries could be controlled.Viscoelastic properties of both injured and non-injured brain tissues were measured using a ramp-hold indentation test.Regions of interests (ROIs) were tested and compared to contralateral corresponding counterparts.Methods introduced in this paper could be easily extended to produce and test a variety of other injured soft biological tissues.
