scholarly journals Targeting riboswitches with synthetic small RNAs for metabolic engineering

2021 ◽  
Author(s):  
Milca Rachel da Costa Ribeiro Lins ◽  
Laura Araujo da Silva Amorim ◽  
Graciely Gomes Correa ◽  
Bruno Willian Picao ◽  
Matthias Mack ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rational Design ◽  
Regulation Of Gene Expression ◽  
Cellular Systems ◽  
Producer Strain ◽  
Natural Systems ◽  
Single Genome ◽  
Non Coding Rnas ◽  
And Function ◽  
Activate Gene

Our growing knowledge of the diversity of non-coding RNAs in natural systems and our deepening knowledge of RNA folding and function have fomented the rational design of RNA regulators. Based on that knowledge, we designed and implemented a small RNA (sRNA) tool to target bacterial riboswitches and activate gene expression. The synthetic sRNA is suitable for the regulation of gene expression both in cell-free and in cellular systems. It targets riboswitches to promote the antitermination folding regardless the cognate metabolite concentration. Therefore, it prevents transcription termination increasing gene expression up to 103-fold. We successfully used sRNA arrays for multiplex targeting of riboswitches. Finally, we used the synthetic sRNA to engineer an improved riboflavin producer strain. The easiness to design and construct, and the fact that the riboswitch-targeting sRNA works as a single genome copy, make it an attractive tool for engineering industrial metabolite-producing strains.

scholarly journals Enhancer RNAs: transcriptional regulators and workmates of NamiRNAs in myogenesis

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Emmanuel Odame ◽  
Yuan Chen ◽  
Shuailong Zheng ◽  
Dinghui Dai ◽  
Bismark Kyei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Transcriptional Regulators ◽  
Chromatin Looping ◽  
Functional Differences ◽  
Non Coding Rnas ◽  
And Function ◽  
Activate Gene ◽  
Promoter Interaction

AbstractmiRNAs are well known to be gene repressors. A newly identified class of miRNAs termed nuclear activating miRNAs (NamiRNAs), transcribed from miRNA loci that exhibit enhancer features, promote gene expression via binding to the promoter and enhancer marker regions of the target genes. Meanwhile, activated enhancers produce endogenous non-coding RNAs (named enhancer RNAs, eRNAs) to activate gene expression. During chromatin looping, transcribed eRNAs interact with NamiRNAs through enhancer-promoter interaction to perform similar functions. Here, we review the functional differences and similarities between eRNAs and NamiRNAs in myogenesis and disease. We also propose models demonstrating their mutual mechanism and function. We conclude that eRNAs are active molecules, transcriptional regulators, and partners of NamiRNAs, rather than mere RNAs produced during enhancer activation.

Through a generation darkly: small RNAs in the gametophyte

2010 ◽  
Vol 38 (2) ◽  
pp. 617-621 ◽  
Author(s):  
Robert T. Grant-Downton
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Small Rnas ◽  
Recent Progress ◽  
Regulation Of Gene Expression ◽  
Non Coding Rnas ◽  
And Function

The various classes of small non-coding RNAs are a fundamentally important component of the transcriptome. These molecules have roles in many essential processes such as regulation of gene expression at the transcriptional and post-transcriptional levels, guidance of DNA methylation and defence against selfish replicators such as transposons. Their diversity and functions in the sporophytic generation of angiosperms is well explored compared with the gametophytic generation, where little is known about them. Recent progress in understanding their abundance, diversity and function in the gametophyte is reviewed.

scholarly journals Construction and investigation of lncRNA-miRNA-mRNA ceRNA network in thymic epithelial neoplasms

2020 ◽  
Author(s):  
Hanxiao Tang ◽  
Shuyu Ge ◽  
Pingping Sun
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Regulation Of Gene Expression ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Protein Coding ◽  
Cerna Network ◽  
Non Coding Rnas ◽  
Epithelial Neoplasms ◽  
And Function

Abstract Background Competing endogenous RNA (ceRNA) networks may be used to relate the functions of protein-coding mRNAs with those of the non-coding RNAs, such as microRNAs (miRNAs) and the long non-coding RNAs (lncRNAs). ceRNAs enable the post-transcriptional regulation of gene expression by competing for the shared miRNAs. However, the role and function of the lncRNA-miRNA-mRNA ceRNA network in thymic epithelial neoplasms (TEN) remains unknown. Methods The miRNA, mRNA, and lncRNA expression profiles of 124 patients with TEN were downloaded from The Cancer Genome Atlas. We identified the differentially expressed (DE) miRNAs, mRNAs, and lncRNAs using the limma package in R software. The GDCRNATools package was used for the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations. Cytoscape software was used to construct the lncRNA-miRNA-mRNA ceRNA network. The Gene Expression Profiling Interactive Analysis platform was used to estimate the overall survival (OS) rates of the patients. Survival curves were analyzed using the log-rank test. Finally, the mRNAs in the ceRNA network were analyzed using the GOplot package in R. Results A total of 1513, 188, and 579 TEN-specific mRNAs, lncRNAs, and miRNAs, respectively, were identified. The lncRNA-miRNA-mRNA ceRNA network was constructed, and included 53 mRNAs, 4 lncRNAs, and 27 miRNAs. A total of 10 DEmRNAs (DLX2, C8orf88, CD38, GATA3, MAL, FOXQ1, FOLH1, NLRP12, HJURP, and ACSM1) and 1 lncRNA (SNHG3) were found to be significantly associated with OS ( P <0.05). Conclusion In this study, we constructed a lncRNA-miRNA-mRNA ceRNA gene regulatory network for TEN, and identified potential prognostic and diagnostic biomarkers, as well as therapeutic targets, for the disease.

scholarly journals Long non-coding RNAs in brain tumors

NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Keisuke Katsushima ◽  
George Jallo ◽  
Charles G Eberhart ◽  
Ranjan J Perera
Keyword(s):  
Gene Expression ◽  
Brain Tumors ◽  
Brain Cancer ◽  
Regulation Of Gene Expression ◽  
Therapeutic Targets ◽  
Diagnostic Biomarkers ◽  
Cancer Pathogenesis ◽  
Current State ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

Abstract Long non-coding RNAs (lncRNAs) have been found to be central players in the epigenetic, transcriptional and post-transcriptional regulation of gene expression. There is an accumulation of evidence on newly discovered lncRNAs, their molecular interactions and their roles in the development and progression of human brain tumors. LncRNAs can have either tumor suppressive or oncogenic functions in different brain cancers, making them attractive therapeutic targets and biomarkers for personalized therapy and precision diagnostics. Here, we summarize the current state of knowledge of the lncRNAs that have been implicated in brain cancer pathogenesis, particularly in gliomas and medulloblastomas. We discuss their epigenetic regulation as well as the prospects of using lncRNAs as diagnostic biomarkers and therapeutic targets in patients with brain tumors.

Detection of Synergistic Combinatorial Perturbations by a Bifurcation-Based Approach

2021 ◽  
Vol 31 (12) ◽  
pp. 2150175
Author(s):  
Min Luo ◽  
Dasong Huang ◽  
Jianfeng Jiao ◽  
Ruiqi Wang
Keyword(s):  
Gene Expression ◽  
Rational Design ◽  
Epithelial To Mesenchymal Transition ◽  
Regulation Of Gene Expression ◽  
Drug Combinations ◽  
Bifurcation Curve ◽  
Combinatorial Regulation ◽  
Mesenchymal Transition ◽  
Combinatorial Control ◽  
Two Parameters

Drug combination has become an attractive strategy against complex diseases, despite the challenges in handling a large number of possible combinations among candidate drugs. How to detect effective drug combinations and determine the dosage of each drug in the combination is still a challenging task. When regarding a drug as a perturbation, we propose a bifurcation-based approach to detect synergistic combinatorial perturbations. In the approach, parameters of a dynamical system are divided into two groups according to their responses to perturbations. By combining two parameters chosen from two groups, three types of combinations can be obtained. Synergism for different perturbation combinations can be detected by relative positions of the bifurcation curve and the isobole. The bifurcation-based approach can be used not only to detect combinatorial perturbations but also to determine their perturbation quantities. To demonstrate the effectiveness of the approach, we apply it to the epithelial-to-mesenchymal transition (EMT) network. The approach has implications for the rational design of drug combinations and other combinatorial control, e.g. combinatorial regulation of gene expression.

scholarly journals The Crosstalk between Acetylation and Phosphorylation: Emerging New Roles for HDAC Inhibitors in the Heart

2018 ◽  
Vol 20 (1) ◽  
pp. 102 ◽  
Author(s):  
Justine Habibian ◽  
Bradley Ferguson
Keyword(s):  
Gene Expression ◽  
Protein Phosphorylation ◽  
Cross Talk ◽  
Electrostatic Interactions ◽  
Regulation Of Gene Expression ◽  
Hdac Inhibitors ◽  
Protein Activity ◽  
Histone Protein ◽  
Signal Transduction Protein ◽  
And Function

Approximately five million United States (U.S.) adults are diagnosed with heart failure (HF), with eight million U.S. adults projected to suffer from HF by 2030. With five-year mortality rates following HF diagnosis approximating 50%, novel therapeutic treatments are needed for HF patients. Pre-clinical animal models of HF have highlighted histone deacetylase (HDAC) inhibitors as efficacious therapeutics that can stop and potentially reverse cardiac remodeling and dysfunction linked with HF development. HDACs remove acetyl groups from nucleosomal histones, altering DNA-histone protein electrostatic interactions in the regulation of gene expression. However, HDACs also remove acetyl groups from non-histone proteins in various tissues. Changes in histone and non-histone protein acetylation plays a key role in protein structure and function that can alter other post translational modifications (PTMs), including protein phosphorylation. Protein phosphorylation is a well described PTM that is important for cardiac signal transduction, protein activity and gene expression, yet the functional role for acetylation-phosphorylation cross-talk in the myocardium remains less clear. This review will focus on the regulation and function for acetylation-phosphorylation cross-talk in the heart, with a focus on the role for HDACs and HDAC inhibitors as regulators of acetyl-phosphorylation cross-talk in the control of cardiac function.

The Role of miR-210 in the Biological System: A Current Overview

2019 ◽  
Vol 84 (6) ◽  
pp. 233-239
Author(s):  
Xu Hui ◽  
Hisham Al-Ward ◽  
Fahmi Shaher ◽  
Chun-Yang Liu ◽  
Ning Liu
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Low Oxygen ◽  
Cellular Functions ◽  
Regulate Gene Expression ◽  
System A ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation ◽  
A Current

<b><i>Background:</i></b> MicroRNAs (miRNAs) represent a group of non-coding RNAs measuring 19–23 nucleotides in length and are recognized as powerful molecules that regulate gene expression in eukaryotic cells. miRNAs stimulate the post-transcriptional regulation of gene expression via direct or indirect mechanisms. <b><i>Summary:</i></b> miR-210 is highly upregulated in cells under hypoxia, thereby revealing its significance to cell endurance. Induction of this mRNA expression is an important feature of the cellular low-oxygen response and the most consistent and vigorous target of HIF. <b><i>Key Message:</i></b> miR-210 is involved in many cellular functions under the effect of HIF-1α, including the cell cycle, DNA repair, immunity and inflammation, angiogenesis, metabolism, and macrophage regulation. It also plays an important regulatory role in T-cell differentiation and stimulation.

scholarly journals xB elements strongly activate gene expression in non-lymphoid cells and function synergistically with NF1 elements

1989 ◽  
Vol 17 (20) ◽  
pp. 8197-8206 ◽  
Author(s):  
Lothar Henninghausen ◽  
Priscilla A. Furth ◽  
Chirstoph W. Pittius
Keyword(s):  
Gene Expression ◽  
Lymphoid Cells ◽  
And Function ◽  
Activate Gene

Misregulation of the Dependence Receptor DCC and its Upstream lincRNA, LOC100287225, in Colorectal Cancer

2015 ◽  
Vol 103 (1) ◽  
pp. 40-43 ◽  
Author(s):  
Mina Kazemzadeh ◽  
Reza Safaralizadeh ◽  
Mohammad Ali HosseinPour feizi ◽  
Mohammad Hossein Somi ◽  
Behrooz Shokoohi
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Regulation Of Gene Expression ◽  
Cellular Processes ◽  
Qrt Pcr ◽  
Cis Regulation ◽  
Tumor Tissues ◽  
Non Coding Rnas ◽  
Colorectal Cancer Patients ◽  
Dependence Receptor

Background Long non-coding RNAs (lncRNAs), a class of regulatory RNAs, play a major role in various cellular processes. Long intergenic non-coding RNAs (lincRNAs), a subclass of lncRNAs, are involved in the trans- and cis-regulation of gene expression. In the case of cis-regulation, by recruiting chromatin-modifying complexes, lincRNAs influence adjacent gene expression. Methods We used quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to evaluate the coexpression of LOC100287225, a lincRNA, and DCC, one of its adjacent genes that is often decreased in colorectal cancer, in pairs of tumor and adjacent tumor-free tissues of 30 colorectal cancer patients. Results The qRT-PCR results revealed the misregulation of these genes during tumorigenesis. Their relative expression levels were significantly lower in tumor tissues than adjacent tumor-free tissues. However, the analysis found no significant correlation between reduced expression of these genes. Conclusions Our study demonstrated the concurrent misregulation of DCC and LOC100287225 in colorectal cancer.

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