Plant microRNAs: master regulator of gene expression mechanism

2015 ◽  
Vol 39 (11) ◽  
pp. 1185-1190 ◽  
Author(s):  
Riddhi Datta ◽  
Soumitra Paul
2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii294-iii295
Author(s):  
Jovana Pavisic ◽  
Chankrit Sethi ◽  
Chris Jones ◽  
Stergios Zacharoulis ◽  
Andrea Califano

Abstract Diffuse intrinsic pontine glioma (DIPG) remains a fatal disease with no effective drugs to date. Mutation-based precision oncology approaches are limited by lack of targetable mutations and genetic heterogeneity. We leveraged systems biology methodologies to discover common targetable disease drivers—master regulator proteins (MRs)—in DIPG to expand treatment options. Using the metaVIPER algorithm, we interrogated an integrated low grade glioma and GBM gene regulatory network with 31 DIPG-gene expression signatures to identify tumor-specific MRs by differential expression of their transcriptional targets. Unsupervised clustering identified MR signatures of upregulated activity in RRM2/TOP2A in 13 patients, CD3D in 5 patients, and MMP7, TACSTD2, RAC2 and SLC15A1/SLC34A2 in individual patients, all of which can be targeted. Notably, intratumoral administration of etoposide by convection enhanced delivery was effective in murine proneural gliomas in which TOP2 was identified as a MR while RRM2—targetable by drugs such as cladribine—has been shown to be a positive regulator of glioma progression whose knock-down inhibits tumor growth. We also prioritized drugs by their ability to reverse MR-activity signatures using a large drug-perturbation database. Patients clustered by predicted drug sensitivities with distinct groups of tumors predicted to respond to proteasome inhibitors, Thiotepa or Volasertib all of which have early evidence in treating gliomas. We will refine this analysis in a multi-institutional study of >100 patient gene expression profiles to define MR signatures driving known biological/molecular disease subtypes, use DIPG cell lines recapitulating common MR architectures to optimize therapy prioritization, and validate our findings in vivo.


2020 ◽  
Vol 13 (1) ◽  
pp. 294
Author(s):  
Khadija Nawaz ◽  
Rimsha Chaudhary ◽  
Ayesha Sarwar ◽  
Bushra Ahmad ◽  
Asma Gul ◽  
...  

Melatonin, a multifunctional signaling molecule, is ubiquitously distributed in different parts of a plant and responsible for stimulating several physiochemical responses against adverse environmental conditions in various plant systems. Melatonin acts as an indoleamine neurotransmitter and is primarily considered as an antioxidant agent that can control reactive oxygen and nitrogen species in plants. Melatonin, being a signaling agent, induces several specific physiological responses in plants that might serve to enhance photosynthesis, growth, carbon fixation, rooting, seed germination and defense against several biotic and abiotic stressors. It also works as an important modulator of gene expression related to plant hormones such as in the metabolism of indole-3-acetic acid, cytokinin, ethylene, gibberellin and auxin carrier proteins. Additionally, the regulation of stress-specific genes and the activation of pathogenesis-related protein and antioxidant enzyme genes under stress conditions make it a more versatile molecule. Because of the diversity of action of melatonin, its role in plant growth, development, behavior and regulation of gene expression it is a plant’s master regulator. This review outlines the main functions of melatonin in the physiology, growth, development and regulation of higher plants. Its role as anti-stressor agent against various abiotic stressors, such as drought, salinity, temperatures, UV radiation and toxic chemicals, is also analyzed critically. Additionally, we have also identified many new aspects where melatonin may have possible roles in plants, for example, its function in improving the storage life and quality of fruits and vegetables, which can be useful in enhancing the environmentally friendly crop production and ensuring food safety.


mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Jan Kampf ◽  
Jan Gerwig ◽  
Kerstin Kruse ◽  
Robert Cleverley ◽  
Miriam Dormeyer ◽  
...  

ABSTRACT Biofilm formation by Bacillus subtilis requires the expression of genes encoding enzymes for extracellular polysaccharide synthesis and for an amyloid-like protein. The master regulator SinR represses all the corresponding genes, and repression of these key biofilm genes is lifted when SinR interacts with its cognate antagonist proteins. The YmdB phosphodiesterase is a recently discovered factor that is involved in the control of SinR activity: cells lacking YmdB exhibit hyperactive SinR and are unable to relieve the repression of the biofilm genes. In this study, we have examined the dynamics of gene expression patterns in wild-type and ymdB mutant cells by microfluidic analysis coupled to time-lapse microscopy. Our results confirm the bistable expression pattern for motility and biofilm genes in the wild-type strain and the loss of biofilm gene expression in the mutant. Moreover, we demonstrated dynamic behavior in subpopulations of the wild-type strain that is characterized by switches in sets of the expressed genes. In order to gain further insights into the role of YmdB, we isolated a set of spontaneous suppressor mutants derived from ymdB mutants that had regained the ability to form complex colonies and biofilms. Interestingly, all of the mutations affected SinR. In some mutants, large genomic regions encompassing sinR were deleted, whereas others had alleles encoding SinR variants. Functional and biochemical studies with these SinR variants revealed how these proteins allowed biofilm gene expression in the ymdB mutant strains. IMPORTANCE Many bacteria are able to choose between two mutually exclusive lifestyles: biofilm formation and motility. In the model bacterium Bacillus subtilis, this choice is made by each individual cell rather than at the population level. The transcriptional repressor SinR is the master regulator in this decision-making process. The regulation of SinR activity involves complex control of its own expression and of its interaction with antagonist proteins. We show that the YmdB phosphodiesterase is required to allow the expression of SinR-repressed genes in a subpopulation of cells and that such subpopulations can switch between different SinR activity states. Suppressor analyses revealed that ymdB mutants readily acquire mutations affecting SinR, thus restoring biofilm formation. These findings suggest that B. subtilis cells experience selective pressure to form the extracellular matrix that is characteristic of biofilms and that YmdB is required for the homeostasis of SinR and/or its antagonists.


2016 ◽  
Vol 10 (01) ◽  
pp. 1750006
Author(s):  
Shaurya Jauhari ◽  
S. A. M. Rizvi

Various algorithms have been devised to mathematically model the dynamic mechanism of the gene expression data. Gillespie’s stochastic simulation (GSSA) has been exceptionally primal for chemical reaction synthesis with future ameliorations. Several other mathematical techniques such as differential equations, thermodynamic models and Boolean models have been implemented to optimally and effectively represent the gene functioning. We present a novel mathematical framework of gene expression, undertaking the mathematical modeling of the transcription and translation phases, which is a detour from conventional modeling approaches. These subprocesses are inherent to every gene expression, which is implicitly an experimental outcome. As we foresee, there can be modeled a generality about some basal translation or transcription values that correspond to a particular assay.


Author(s):  
Daniele Mercatelli ◽  
Gonzalo Lopez-Garcia ◽  
Federico M. Giorgi

AbstractMotivationGene Network Inference and Master Regulator Analysis (MRA) have been widely adopted to define specific transcriptional perturbations from gene expression signatures. Several tools exist to perform such analyses, but most require a computer cluster or large amounts of RAM to be executed.ResultsWe developed corto, a fast and lightweight R package to infer gene networks and perform MRA from gene expression data, with optional corrections for Copy Number Variations (CNVs) and able to run on signatures generated from RNA-Seq or ATAC-Seq data. We extensively benchmarked it to infer context-specific gene networks in 39 human tumor and 27 normal tissue datasets.AvailabilityCross-platform and multi-threaded R package on CRAN (stable version) https://cran.rproject.org/package=corto and Github (development release) https://github.com/federicogiorgi/[email protected]


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