scholarly journals An Exportin-1–dependent microRNA biogenesis pathway during human cell quiescence

2017 ◽  
Vol 114 (25) ◽  
pp. E4961-E4970 ◽  
Author(s):  
Ivan Martinez ◽  
Karen E. Hayes ◽  
Jamie A. Barr ◽  
Abby D. Harold ◽  
Mingyi Xie ◽  
...  
Keyword(s):  
Cell Biology ◽  
Alternative Pathway ◽  
Human Fibroblasts ◽  
Cellular Growth ◽  
Mirna Biogenesis ◽  
Mirna Processing ◽  
Quiescent Cells ◽  
Cellular Quiescence ◽  
Processing Factors ◽  
Mirna Biogenesis Pathway

The reversible state of proliferative arrest known as “cellular quiescence” plays an important role in tissue homeostasis and stem cell biology. By analyzing the expression of miRNAs and miRNA-processing factors during quiescence in primary human fibroblasts, we identified a group of miRNAs that are induced during quiescence despite markedly reduced expression of Exportin-5, a protein required for canonical miRNA biogenesis. The biogenesis of these quiescence-induced miRNAs is independent of Exportin-5 and depends instead on Exportin-1. Moreover, these quiescence-induced primary miRNAs (pri-miRNAs) are modified with a 2,2,7-trimethylguanosine (TMG)-cap, which is known to bind Exportin-1, and knockdown of Exportin-1 or trimethylguanosine synthase 1, responsible for (TMG)-capping, inhibits their biogenesis. Surprisingly, in quiescent cells Exportin-1–dependent pri-miR-34a is present in the cytoplasm together with a small isoform of Drosha, implying the existence of a different miRNA processing pathway in these cells. Our findings suggest that during quiescence the canonical miRNA biogenesis pathway is down-regulated and specific miRNAs are generated by an alternative pathway to regulate genes involved in cellular growth arrest.

MicroRNA annotation in plants: current status and challenges

2021 ◽  
Author(s):  
Yongxin Zhao ◽  
Zheng Kuang ◽  
Ying Wang ◽  
Lei Li ◽  
Xiaozeng Yang
Keyword(s):  
Small Rna ◽  
Signal To Noise Ratio ◽  
Current Status ◽  
Mirna Biogenesis ◽  
Plant Mirnas ◽  
Signal To Noise ◽  
Advantages And Disadvantages ◽  
Plant Mirna ◽  
History Of ◽  
Mirna Biogenesis Pathway

Abstract Last two decades, the studies on microRNAs (miRNAs) and the numbers of annotated miRNAs in plants and animals have surged. Herein, we reviewed the current progress and challenges of miRNA annotation in plants. Via the comparison of plant and animal miRNAs, we pinpointed out the difficulties on plant miRNA annotation and proposed potential solutions. In terms of recalling the history of methods and criteria in plant miRNA annotation, we detailed how the major progresses made and evolved. By collecting and categorizing bioinformatics tools for plant miRNA annotation, we surveyed their advantages and disadvantages, especially for ones with the principle of mimicking the miRNA biogenesis pathway by parsing deeply sequenced small RNA (sRNA) libraries. In addition, we summarized all available databases hosting plant miRNAs, and posted the potential optimization solutions such as how to increase the signal-to-noise ratio (SNR) in these databases. Finally, we discussed the challenges and perspectives of plant miRNA annotations, and indicated the possibilities offered by an all-in-one tool and platform according to the integration of artificial intelligence.

scholarly journals The miRNA biogenesis pathway prevents inappropriate expression of injury response genes in developing and adult Schwann cells

Glia ◽  
2018 ◽  
Vol 66 (12) ◽  
pp. 2632-2644 ◽  
Author(s):  
Deniz Gökbuget ◽  
Jorge A. Pereira ◽  
Lennart Opitz ◽  
Dominik Christe ◽  
Tobias Kessler ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Mirna Biogenesis ◽  
Injury Response ◽  
Inappropriate Expression ◽  
Mirna Biogenesis Pathway

scholarly journals Growth of immortal simian virus 40 tsA-transformed human fibroblasts is temperature dependent.

1989 ◽  
Vol 9 (7) ◽  
pp. 3093-3096 ◽  
Author(s):  
R L Radna ◽  
Y Caton ◽  
K K Jha ◽  
P Kaplan ◽  
G Li ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Fibroblasts ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Cellular Aging ◽  
Cellular Growth ◽  
Viral Gene ◽  
Large T Antigen ◽  
Temperature Dependent

Simian virus 40 (SV40)-mediated transformation of human fibroblasts offers an experimental system for studying both carcinogenesis and cellular aging, since such transformants show the typical features of altered cellular growth but still have a limited life span in culture and undergo senescence. We have previously demonstrated (D. S. Neufeld, S. Ripley, A. Henderson, and H. L. Ozer, Mol. Cell. Biol. 7:2794-2802, 1987) that transformants generated with origin-defective mutants of SV40 show an increased frequency of overcoming senescence and becoming immortal. To clarify further the role of large T antigen, we have generated immortalized transformants by using origin-defective mutants of SV40 encoding a heat-labile large T antigen (tsA58 transformants). At a temperature permissive for large-T-antigen function (35 degrees C), the cell line AR5 had properties resembling those of cell lines transformed with wild-type SV40. However, the AR5 cells were unable to proliferate or form colonies at temperatures restrictive for large-T-antigen function (39 degrees C), demonstrating a continuous need for large T antigen even in immortalized human fibroblasts. Such immortal temperature-dependent transformants should be useful cell lines for the identification of other cellular or viral gene products that induce cell proliferation in human cells.

scholarly journals An Algorithm for Cellular Reprogramming

2017 ◽  
Author(s):  
Scott Ronquist ◽  
Geoff Patterson ◽  
Markus Brown ◽  
Stephen Lindsly ◽  
Haiming Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Biology ◽  
Human Fibroblasts ◽  
Cell Types ◽  
Approximate Model ◽  
Cellular Reprogramming ◽  
Biological Processes ◽  
Moderate Complexity

AbstractThe day we understand the time evolution of subcellular elements at a level of detail comparable to physical systems governed by Newton’s laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology, providing data-guided frameworks that allow us to develop better predictions about, and methods for, control over specific biological processes and system-wide cell behavior. In this paper, we describe an approach to optimizing the use of transcription factors (TFs) in the context of cellular reprogramming. We construct an approximate model for the natural evolution of a cell cycle synchronized population of human fibroblasts, based on data obtained by sampling the expression of 22,083 genes at several time points along the cell cycle. In order to arrive at a model of moderate complexity, we cluster gene expression based on the division of the genome into topologically associating domains (TADs) and then model the dynamics of the TAD expression levels. Based on this dynamical model and known bioinformatics, such as transcription factor binding sites (TFBS) and functions, we develop a methodology for identifying the top transcription factor candidates for a specific cellular reprogramming task. The approach used is based on a device commonly used in optimal control. Our data-guided methodology identifies a number of transcription factors previously validated for reprogramming and/or natural differentiation. Our findings highlight the immense potential of dynamical models, mathematics, and data-guided methodologies for improving strategies for control over biological processes.Significance StatementReprogramming the human genome toward any desirable state is within reach; application of select transcription factors drives cell types toward different lineages in many settings. We introduce the concept of data-guided control in building a universal algorithm for directly reprogramming any human cell type into any other type. Our algorithm is based on time series genome transcription and architecture data and known regulatory activities of transcription factors, with natural dimension reduction using genome architectural features. Our algorithm predicts known reprogramming factors, top candidates for new settings, and ideal timing for application of transcription factors. This framework can be used to develop strategies for tissue regeneration, cancer cell reprogramming, and control of dynamical systems beyond cell biology.

Functional characteristics of PMJ2-R macrophages

2020 ◽  
Vol 18 (4) ◽  
pp. 133-137
Author(s):  
P.M. Kozhin ◽  
◽  
A.L. Rusanov ◽  
O.O. Shoshina ◽  
N.G. Luzgina ◽  
...  
Keyword(s):  
Cell Biology ◽  
Alternative Pathway ◽  
Peritoneal Macrophages ◽  
Alternative Activation ◽  
M2 Macrophages ◽  
Phagocytic Cells ◽  
Phenotypic Properties ◽  
M1 Macrophages ◽  
Oxidized Dextran ◽  
Tnf Α

Objective. To evaluate the ability of PMJ2-R cells for classical and alternative activation and to assess the effect of oxidized dextran on the functional status of polarized cells of this line. OD is a promising lysosomotropic agent used for targeted drug delivery to phagocytic cells. Materials and methods. We analyzed ability of immortalized murine peritoneal macrophages PMJ2R (ATCC CRL2458) to classical and alternative polarization, including that upon exposure to OD. We used real-time polymerase chain reaction to assess gene expression of competing arginine pathways. The capacity of phagocytes to engulf zymosan granules was evaluated using fluorescence microscopy. Results. We observed metabolic changes in PMJ2-R cells following their classical and alternative activation; these changes were typical of M1 and M2 macrophages, respectively. M1 macrophages demonstrated most active phagocytosis, while the activity of phagocytosis in M2 macrophages increased dose-dependently upon AD exposure. OD upregulates production of proinflammatory cytokine TNF-α in intact PMJ2-R cells and M1 macrophages. Conclusion. PMJ2-R cells have the capacity to phagocytose particles, can be polarized via the classical and alternative pathway, can modulate their functional activity in response to OD (a macrophagotropic substance), and exhibit the main phenotypic properties typical of peritoneal macrophages from C57Bl/6J mice. Therefore, cells of this line can be used as model cells in the investigation of phagocytic cell biology and pathology. Key words: alternative activation, classical activation, oxidized dextran, peritoneal macrophages, phagocytosis, C57Bl/6J, PMJ2-R

scholarly journals SERRATE interacts with the nuclear exosome targeting (NEXT) complex to degrade primary miRNA precursors in Arabidopsis

2020 ◽  
Vol 48 (12) ◽  
pp. 6839-6854 ◽  
Author(s):  
Mateusz Bajczyk ◽  
Heike Lange ◽  
Dawid Bielewicz ◽  
Lukasz Szewc ◽  
Susheel S Bhat ◽  
...  
Keyword(s):  
Rna Binding ◽  
Mature Mirnas ◽  
Mirna Biogenesis ◽  
Processing Efficiency ◽  
Developmental Defects ◽  
Rna Surveillance ◽  
Mirna Processing ◽  
Rna Targets ◽  
Nuclear Exosome ◽  
Mirna Degradation

Abstract SERRATE/ARS2 is a conserved RNA effector protein involved in transcription, processing and export of different types of RNAs. In Arabidopsis, the best-studied function of SERRATE (SE) is to promote miRNA processing. Here, we report that SE interacts with the nuclear exosome targeting (NEXT) complex, comprising the RNA helicase HEN2, the RNA binding protein RBM7 and one of the two zinc-knuckle proteins ZCCHC8A/ZCCHC8B. The identification of common targets of SE and HEN2 by RNA-seq supports the idea that SE cooperates with NEXT for RNA surveillance by the nuclear exosome. Among the RNA targets accumulating in absence of SE or NEXT are miRNA precursors. Loss of NEXT components results in the accumulation of pri-miRNAs without affecting levels of miRNAs, indicating that NEXT is, unlike SE, not required for miRNA processing. As compared to se-2, se-2 hen2-2 double mutants showed increased accumulation of pri-miRNAs, but partially restored levels of mature miRNAs and attenuated developmental defects. We propose that the slow degradation of pri-miRNAs caused by loss of HEN2 compensates for the poor miRNA processing efficiency in se-2 mutants, and that SE regulates miRNA biogenesis through its double contribution in promoting miRNA processing but also pri-miRNA degradation through the recruitment of the NEXT complex.

scholarly journals MicroRNA-processing Enzymes Are Essential for Survival and Function of Mature Retinal Pigmented Epithelial Cells in Mice

2017 ◽  
Vol 292 (8) ◽  
pp. 3366-3378 ◽  
Author(s):  
Thomas R. Sundermeier ◽  
Sanae Sakami ◽  
Bhubanananda Sahu ◽  
Scott J. Howell ◽  
Songqi Gao ◽  
...  
Keyword(s):  
Cell Death ◽  
Vision Loss ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Mirna Biogenesis ◽  
Mirna Processing ◽  
Processing Enzymes ◽  
Age Related ◽  
Death And Loss ◽  
And Function

Age-related macular degeneration (AMD) is a major cause of irreversible vision loss. The neovascular or “wet” form of AMD can be treated to varying degrees with anti-angiogenic drugs, but geographic atrophy (GA) is an advanced stage of the more prevalent “dry” form of AMD for which there is no effective treatment. Development of GA has been linked to loss of the microRNA (miRNA)-processing enzyme DICER1 in the mature retinal pigmented epithelium (RPE). This loss results in the accumulation of toxic transcripts of Alu transposable elements, which activate the NLRP3 inflammasome and additional downstream pathways that compromise the integrity and function of the RPE. However, it remains unclear whether the loss of miRNA processing and subsequent gene regulation in the RPE due to DICER1 deficiency also contributes to RPE cell death. To clarify the role of miRNAs in RPE cells, we used two different mature RPE cell-specific Cre recombinase drivers to inactivate either Dicer1 or DiGeorge syndrome critical region 8 (Dgcr8), thus removing RPE miRNA regulatory activity in mice by disrupting two independent and essential steps of miRNA biogenesis. In contrast with prior studies, we found that the loss of each factor independently led to strikingly similar defects in the survival and function of the RPE and retina. These results suggest that the loss of miRNAs also contributes to RPE cell death and loss of visual function and could affect the pathology of dry AMD.

Effect of cellular growth state on indices of n − 6 polyunsaturated fatty acid status in human fibroblasts

1990 ◽  
Vol 68 (4) ◽  
pp. 819-822 ◽  
Author(s):  
William J. Bettger ◽  
Eric R. Driscoll ◽  
Soverin Karmiol
Keyword(s):  
Fatty Acid ◽  
Serum Concentration ◽  
Polyunsaturated Fatty Acid ◽  
Human Fibroblasts ◽  
Cellular Growth ◽  
Medium Density ◽  
Fatty Acid Status ◽  
Growth State ◽  
Cell Monolayers ◽  
Acid Status

A 2 × 2 design was employed to examine the effect of cellular growth state and medium serum concentration on potential indices of n − 6 polyunsaturated fatty acid (PUFA) status in human skin fibroblasts. The cells were cultured either as nonmultiplying cell monolayers or as medium-density, log-phase multiplying cells. An interaction of cellular growth state and medium serum concentration influenced the accumulation of 20:3(n − 9), but not 22:3(n − 9), in the cellular phospholipids. The 20:3(n − 9)/20:4(n − 6) ratio was the most sensitive index of n − 6 PUFA status; however, the ratio was significantly affected by cellular growth state. The 22:3(n − 9)/22:4(n − 6) ratio appears to be an index of n − 6 PUFA status in fibroblasts that is not significantly affected by the growth state of cells.Key words: n − 9 polyunsaturated fatty acids, fibroblasts, cell culture.

scholarly journals The seasonal dynamics of bud dormancy in grapevine suggest a regulated checkpoint prior to acclimation

2021 ◽  
Author(s):  
Yazhini Velappan ◽  
Tinashe G Chabikwa ◽  
John A Considine ◽  
Patricia Agudelo-Romero ◽  
Christine H Foyer ◽  
...  
Keyword(s):  
Cellular Growth ◽  
Bud Dormancy ◽  
Bud Burst ◽  
Transcriptome Data ◽  
Seasonal Plasticity ◽  
Bud Set ◽  
Cellular Quiescence ◽  
Approaches To Study ◽  
Bud Respiration ◽  
Transcription Data

ABSTRACTGrapevine (Vitis vinifera L.) displays wide plasticity to climate and seasonality, ranging from strongly deciduous to evergreen. Understanding the physiology of decisions to grow or quiesce is critical for improved crop management, prediction, and the adaptability of production to alternative climate scenarios. The perenniating bud (N+2) is a major economic unit and focus of study. Here we investigated the physiology and transcriptome of cv. Merlot buds grown in a temperate maritime climate from summer to spring in two consecutive years. The changes in bud respiration, hydration and internal tissue oxygen data were consistent with the transcriptome data. ABA-responsive gene processes prevailed upon the transition to a deep metabolic and cellular quiescence in the bud during autumn. Light, together with hypoxia and redox signalling presided over the resumption of nuclear and cellular growth in the transition to spring. Comparisons with transcriptome data from bud burst studies revealed a number of regulatory candidates for the orderly resumption of growth in spring, including components that may integrate light and temperature signalling. Importantly however, the bud burst forcing data, which is widely used as a measure of bud dormancy, were not consistent with the physiological and transcription data. We hypothesise the existence of a physiological checkpoint following bud set in summer, which if not met results in extreme quiescence. Collectively this is the most integrated developmental dataset of the latent bud of cultivated grapevine, and establishes a platform for systems approaches to study seasonal plasticity.One sentence summaryPhysiology and transcriptome data provide strong evidence of a regulatory checkpoint prior to acclimation and dormancy in latent grapevine buds.

scholarly journals Cell cycle-independent integration of stress signals promotes Non-G1/G0 quiescence entry

2021 ◽  
Author(s):  
Orlando Argüello-Miranda ◽  
Ashley Marchand ◽  
Taylor Kennedy ◽  
Marielle AX Russo ◽  
Jungsik Noh
Keyword(s):  
Machine Learning ◽  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Transcription Factors ◽  
Kinase Activity ◽  
Nuclear Accumulation ◽  
Quiescent Cells ◽  
Developmental Mechanisms ◽  
Cellular Quiescence ◽  
Stress Signals

AbstractCellular quiescence is a non-proliferative state required for cell survival under stress and during development. In most quiescent cells, proliferation is stopped in a reversible state of low Cdk1 kinase activity; in many organisms, however, quiescent states with high Cdk1 activity can also be established through still uncharacterized stress or developmental mechanisms. Here, we used a microfluidics approach coupled to phenotypic classification by machine learning to identify stress pathways associated with starvation-triggered high-Cdk1 quiescent states in Saccharomyces cerevisiae. We found that low- and high-Cdk1 quiescent states shared a core of stress-associated processes, such as autophagy, protein aggregation, and mitochondrial upregulation, but differed in the nuclear accumulation of the stress transcription factors Xbp1, Gln3, and Sfp1. The decision between low- or high-Cdk1 quiescence was controlled by cell cycle-independent accumulation of Xbp1, which acted as a time-delayed integrator of the duration of stress stimuli. Our results show how cell cycle-independent stress-activated factors promote cellular quiescence outside of G1/G0.

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