scholarly journals Regulatory landscape of the Hox transcriptome

2018 ◽  
Vol 62 (11-12) ◽  
pp. 693-704 ◽  
Author(s):  
Ana Casaca ◽  
Gabriel M. Hauswirth ◽  
Heidi Bildsoe ◽  
Moisés Mallo ◽  
Edwina McGlinn
Keyword(s):  
Translational Control ◽  
Noncoding Rna ◽  
Current Knowledge ◽  
Developmental Systems ◽  
Rna Regulation ◽  
Polycistronic Transcription ◽  
Hox Protein ◽  
Post Transcriptional Regulation ◽  
Protein Output ◽  
Cluster Gene

Precise regulation of Hox gene activity is essential to achieve proper control of animal embryonic development and to avoid generation of a variety of malignancies. This is a multilayered process, including complex polycistronic transcription, RNA processing, microRNA repression, long noncoding RNA regulation and sequence-specific translational control, acting together to achieve robust quantitative and qualitative Hox protein output. For many such mechanisms, the Hox cluster gene network has turned out to serve as a paradigmatic model for their study. In this review, we discuss current knowledge of how the different layers of post-transcriptional regulation and the production of a variety of noncoding RNA species control Hox output, and how this shapes formation of developmental systems that are reproducibly patterned by complex Hox networks.

scholarly journals Signal Transduction and Regulatory Mechanisms Involved in Control of the σS (RpoS) Subunit of RNA Polymerase

2002 ◽  
Vol 66 (3) ◽  
pp. 373-395 ◽  
Author(s):  
Regine Hengge-Aronis
Keyword(s):  
Rna Polymerase ◽  
Translational Control ◽  
Current Knowledge ◽  
Response Regulator ◽  
Regulatory System ◽  
Stress Conditions ◽  
Acidic Ph ◽  
High Osmolarity ◽  
Multiple Signal ◽  
Rpos Mrna

SUMMARY The σS (RpoS) subunit of RNA polymerase is the master regulator of the general stress response in Escherichia coli and related bacteria. While rapidly growing cells contain very little σS, exposure to many different stress conditions results in rapid and strong σS induction. Consequently, transcription of numerous σS-dependent genes is activated, many of which encode gene products with stress-protective functions. Multiple signal integration in the control of the cellular σS level is achieved by rpoS transcriptional and translational control as well as by regulated σS proteolysis, with various stress conditions differentially affecting these levels of σS control. Thus, a reduced growth rate results in increased rpoS transcription whereas high osmolarity, low temperature, acidic pH, and some late-log-phase signals stimulate the translation of already present rpoS mRNA. In addition, carbon starvation, high osmolarity, acidic pH, and high temperature result in stabilization of σS, which, under nonstress conditions, is degraded with a half-life of one to several minutes. Important cis-regulatory determinants as well as trans-acting regulatory factors involved at all levels of σS regulation have been identified. rpoS translation is controlled by several proteins (Hfq and HU) and small regulatory RNAs that probably affect the secondary structure of rpoS mRNA. For σS proteolysis, the response regulator RssB is essential. RssB is a specific direct σS recognition factor, whose affinity for σS is modulated by phosphorylation of its receiver domain. RssB delivers σS to the ClpXP protease, where σS is unfolded and completely degraded. This review summarizes our current knowledge about the molecular functions and interactions of these components and tries to establish a framework for further research on the mode of multiple signal input into this complex regulatory system.

scholarly journals The Distinctive Regulation of Cyanobacterial Glutamine Synthetase

Life ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 52 ◽  
Author(s):  
Paul Bolay ◽  
M. Muro-Pastor ◽  
Francisco Florencio ◽  
Stephan Klähn
Keyword(s):  
Glutamine Synthetase ◽  
Gene Expression Regulation ◽  
Feedback Inhibition ◽  
Current Knowledge ◽  
Transcriptional Level ◽  
Distinctive Features ◽  
Small Proteins ◽  
Regulatory Systems ◽  
Covalent Modifications ◽  
Post Transcriptional Regulation

Glutamine synthetase (GS) features prominently in bacterial nitrogen assimilation as it catalyzes the entry of bioavailable nitrogen in form of ammonium into cellular metabolism. The classic example, the comprehensively characterized GS of enterobacteria, is subject to exquisite regulation at multiple levels, among them gene expression regulation to control GS abundance, as well as feedback inhibition and covalent modifications to control enzyme activity. Intriguingly, the GS of the ecologically important clade of cyanobacteria features fundamentally different regulatory systems to those of most prokaryotes. These include the interaction with small proteins, the so-called inactivating factors (IFs) that inhibit GS linearly with their abundance. In addition to this protein interaction-based regulation of GS activity, cyanobacteria use alternative elements to control the synthesis of GS and IFs at the transcriptional level. Moreover, cyanobacteria evolved unique RNA-based regulatory mechanisms such as glutamine riboswitches to tightly tune IF abundance. In this review, we aim to outline the current knowledge on the distinctive features of the cyanobacterial GS encompassing the overall control of its activity, sensing the nitrogen status, transcriptional and post-transcriptional regulation, as well as strain-specific differences.

Unique Archaeal Small RNAs

2018 ◽  
Vol 52 (1) ◽  
pp. 465-487 ◽  
Author(s):  
José Vicente Gomes-Filho ◽  
Michael Daume ◽  
Lennart Randau
Keyword(s):  
Noncoding Rna ◽  
Genome Rearrangement ◽  
Rna Binding ◽  
Elevated Temperatures ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Extreme Environments ◽  
Noncoding Rnas ◽  
Hyperthermophilic Archaea ◽  
Rna Modification

Advances in genome-wide sequence technologies allow for detailed insights into the complexity of RNA landscapes of organisms from all three domains of life. Recent analyses of archaeal transcriptomes identified interaction and regulation networks of noncoding RNAs in this understudied domain. Here, we review current knowledge of small, noncoding RNAs with important functions for the archaeal lifestyle, which often requires adaptation to extreme environments. One focus is RNA metabolism at elevated temperatures in hyperthermophilic archaea, which reveals elevated amounts of RNA-guided RNA modification and virus defense strategies. Genome rearrangement events result in unique fragmentation patterns of noncoding RNA genes that require elaborate maturation pathways to yield functional transcripts. RNA-binding proteins, e.g., L7Ae and LSm, are important for many posttranscriptional control functions of RNA molecules in archaeal cells. We also discuss recent insights into the regulatory potential of their noncoding RNA partners.

scholarly journals The emerging role of microRNAs in bone remodeling and its therapeutic implications for osteoporosis

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Qianyun Feng ◽  
Sheng Zheng ◽  
Jia Zheng
Keyword(s):  
Bone Remodeling ◽  
Noncoding Rna ◽  
Target Genes ◽  
Epigenetic Modification ◽  
Therapeutic Implications ◽  
Small Noncoding Rna ◽  
Genetic And Environmental Factors ◽  
Underlying Mechanisms ◽  
Post Transcriptional Regulation

Osteoporosis, a common and multifactorial disease, is influenced by genetic factors and environments. However, the pathogenesis of osteoporosis has not been fully elucidated yet. Recently, emerging evidence suggests that epigenetic modifications may be the underlying mechanisms that link genetic and environmental factors with increased risks of osteoporosis and bone fracture. MicroRNA (miRNA), a major category of small noncoding RNA with 20–22 bases in length, is recognized as one important epigenetic modification. It can mediate post-transcriptional regulation of target genes with cell differentiation and apoptosis. In this review, we aimed to profile the role of miRNA in bone remodeling and its therapeutic implications for osteoporosis. A deeper insight into the role of miRNA in bone remodeling and osteoporosis can provide unique opportunities to develop a novel diagnostic and therapeutic approach of osteoporosis.

Missing links — epigenetic regulators of the pancreatic cancer–associated inflammation

2021 ◽  
Vol 135 (10) ◽  
pp. 1289-1293
Author(s):  
Gregor Werba ◽  
Tamas A. Gonda
Keyword(s):  
Pancreatic Cancer ◽  
Noncoding Rna ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Therapeutic Interventions ◽  
Ductal Adenocarcinoma ◽  
Gastrointestinal Cancers ◽  
Novel Treatment ◽  
Epigenetic Regulator ◽  
Novel Treatment Strategies

Abstract Pancreatic ductal adenocarcinoma (PDAC) features a hostile tumor microenvironment (TME) that renders it remarkably resistant to most therapeutic interventions. Consequently, survival remains among the poorest compared with other gastrointestinal cancers. Concerted efforts are underway to decipher the complex PDAC TME, break down barriers to efficacious therapies and identify novel treatment strategies. In the recent Clinical Science, Li and colleagues identify the long noncoding RNA KLHDC7B-DT as a crucial epigenetic regulator of IL-6 transcription in PDAC and illustrate its potent influences on the pancreatic TME. In this commentary, we introduce epigenetics in pancreatic cancer and put the findings by Li et al. in context with current knowledge.

scholarly journals The Intricate Interplay between Epigenetic Events, Alternative Splicing and Noncoding RNA Deregulation in Colorectal Cancer

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 929 ◽  
Author(s):  
Raheleh Amirkhah ◽  
Hojjat Naderi-Meshkin ◽  
Jaynish Shah ◽  
Philip Dunne ◽  
Ulf Schmitz
Keyword(s):  
Colorectal Cancer ◽  
Alternative Splicing ◽  
Noncoding Rna ◽  
Tumour Microenvironment ◽  
Rna Regulation ◽  
Non Coding Rna ◽  
Epigenetic Events ◽  
Transcriptional Gene Regulation ◽  
Aberrant Dna Methylation ◽  
And Function

Colorectal cancer (CRC) results from a transformation of colonic epithelial cells into adenocarcinoma cells due to genetic and epigenetic instabilities, alongside remodelling of the surrounding stromal tumour microenvironment. Epithelial-specific epigenetic variations escorting this process include chromatin remodelling, histone modifications and aberrant DNA methylation, which influence gene expression, alternative splicing and function of non-coding RNA. In this review, we first highlight epigenetic modulators, modifiers and mediators in CRC, then we elaborate on causes and consequences of epigenetic alterations in CRC pathogenesis alongside an appraisal of the complex feedback mechanisms realized through alternative splicing and non-coding RNA regulation. An emphasis in our review is put on how this intricate network of epigenetic and post-transcriptional gene regulation evolves during the initiation, progression and metastasis formation in CRC.

scholarly journals Radiation-Induced Normal Tissue Damage: Oxidative Stress and Epigenetic Mechanisms

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jinlong Wei ◽  
Bin Wang ◽  
Huanhuan Wang ◽  
Lingbin Meng ◽  
Qin Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Tissue Damage ◽  
Normal Tissue ◽  
Noncoding Rna ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Redox System ◽  
Epigenetic Mechanisms ◽  
Rna Regulation ◽  
Normal Tissue Damage ◽  
Radiation Induced

Radiotherapy (RT) is currently one of the leading treatments for various cancers; however, it may cause damage to healthy tissue, with both short-term and long-term side effects. Severe radiation-induced normal tissue damage (RINTD) frequently has a significant influence on the progress of RT and the survival and prognosis of patients. The redox system has been shown to play an important role in the early and late effects of RINTD. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the main sources of RINTD. The free radicals produced by irradiation can upregulate several enzymes including nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), lipoxygenases (LOXs), nitric oxide synthase (NOS), and cyclooxygenases (COXs). These enzymes are expressed in distinct ways in various cells, tissues, and organs and participate in the RINTD process through different regulatory mechanisms. In recent years, several studies have demonstrated that epigenetic modulators play an important role in the RINTD process. Epigenetic modifications primarily contain noncoding RNA regulation, histone modifications, and DNA methylation. In this article, we will review the role of oxidative stress and epigenetic mechanisms in radiation damage, and explore possible prophylactic and therapeutic strategies for RINTD.

scholarly journals Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-23 ◽  
Author(s):  
Arun Samidurai ◽  
Rakesh C. Kukreja ◽  
Anindita Das
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Signaling Pathway ◽  
Noncoding Rna ◽  
Current Knowledge ◽  
Mammalian Target Of Rapamycin ◽  
Vital Role ◽  
Mtor Signaling ◽  
Cellular Growth ◽  
Mtor Signaling Pathway

Mechanistic/mammalian target of rapamycin (mTOR), an atypical serine/threonine kinase of the phosphoinositide 3-kinase- (PI3K-) related kinase family, elicits a vital role in diverse cellular processes, including cellular growth, proliferation, survival, protein synthesis, autophagy, and metabolism. In the cardiovascular system, the mTOR signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of both physiological and pathological processes. MicroRNAs (miRs), a class of short noncoding RNA, are an emerging intricate posttranscriptional modulator of critical gene expression for the development and maintenance of homeostasis across a wide array of tissues, including the cardiovascular system. Over the last decade, numerous studies have revealed an interplay between miRNAs and the mTOR signaling circuit in the different cardiovascular pathophysiology, like myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation, and atherosclerosis. In this review, we provide a comprehensive state of the current knowledge regarding the mechanisms of interactions between the mTOR signaling pathway and miRs. We have also highlighted the latest advances on mTOR-targeted therapy in clinical trials and the new perspective therapeutic strategies with mTOR-targeting miRs in cardiovascular diseases.

scholarly journals Novel Translation Initiation Regulation Mechanism in Escherichia coli ptrB Mediated by a 5′-Terminal AUG

2017 ◽  
Vol 199 (14) ◽  
Author(s):  
Heather J. Beck ◽  
Gary R. Janssen
Keyword(s):  
Escherichia Coli ◽  
Translation Initiation ◽  
Translational Regulation ◽  
Current Knowledge ◽  
Upstream Open Reading Frame ◽  
Model Organisms ◽  
Regulation Mechanism ◽  
Rna Regulation ◽  
Content Type ◽  
E Coli

ABSTRACT Alternative translation initiation mechanisms, distinct from the Shine-Dalgarno (SD) sequence-dependent mechanism, are more prevalent in bacteria than once anticipated. Translation of Escherichia coli ptrB instead requires an AUG triplet at the 5′ terminus of its mRNA. The 5′-terminal AUG (5′-uAUG) acts as a ribosomal recognition signal to attract ribosomes to the ptrB mRNA rather than functioning as an initiation codon to support translation of an upstream open reading frame. ptrB expression exhibits a stronger dependence on the 5′-uAUG than the predicted SD sequence; however, strengthening the predicted ptrB SD sequence relieves the necessity for the 5′-uAUG. Additional sequences within the ptrB 5′ untranslated region (5′-UTR) work cumulatively with the 5′-uAUG to control expression of the downstream ptrB coding sequence (CDS), thereby compensating for the weak SD sequence. Replacement of 5′-UTRs from other mRNAs with the ptrB 5′-UTR sequence showed a similar dependence on the 5′-uAUG for CDS expression, suggesting that the regulatory features contained within the ptrB 5′-UTR are sufficient to control the expression of other E. coli CDSs. Demonstration that the 5′-uAUG present on the ptrB leader mRNA is involved in ribosome binding and expression of the downstream ptrB CDS revealed a novel form of translational regulation. Due to the abundance of AUG triplets at the 5′ termini of E. coli mRNAs and the ability of ptrB 5′-UTR regulation to function independently of gene context, the regulatory effects of 5′-uAUGs on downstream CDSs may be widespread throughout the E. coli genome. IMPORTANCE As the field of synthetic biology continues to grow, a complete understanding of basic biological principles will be necessary. The increasing complexity of the synthetic systems highlights the gaps in our current knowledge of RNA regulation. This study demonstrates that there are novel ways to regulate canonical Shine-Dalgarno-led mRNAs in Escherichia coli, illustrating that our understanding of the fundamental processes of translation and RNA regulation is still incomplete. Even for E. coli, one of the most-studied model organisms, genes with translation initiation mechanisms that do not fit the canonical Shine-Dalgarno sequence paradigm are being revealed. Uncovering diverse mechanisms that control translational expression will allow synthetic biologists to finely tune protein production of desired gene products.

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