scholarly journals Roles of miR-17-92 Cluster in Cardiovascular Development and Common Diseases

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Huanyu Gu ◽  
Zhuyuan Liu ◽  
Lei Zhou
Keyword(s):  
Cardiovascular Disease ◽  
Small Rna ◽  
Normal Development ◽  
Cardiac Development ◽  
Critical Role ◽  
Tissue Homeostasis ◽  
Mirna Cluster ◽  
Cardiovascular Development ◽  
Rna Molecules ◽  
Precise Control

MicroRNAs (miRNAs and miRs) are a large class of noncoding, single-stranded, small RNA molecules. The precise control of their expression is essential for keeping tissue homeostasis and normal development of organisms. Thus, unbalanced expression of miRNAs is a hallmark of many diseases. Two to dozens of miRNAs can form into a miRNA cluster, and the miR-17-92 cluster is one of them. Although firstly described as an oncogenic miRNA cluster, the miR-17-92 cluster has also been found to play critical role in normal cardiac development and cardiovascular disease. This review focuses on the characteristics and functions of miR-17-92 cluster in heart.

scholarly journals Mechanosensing Piezo channels in tissue homeostasis including their role in lungs

2018 ◽  
Vol 8 (2) ◽  
pp. 204589401876739 ◽  
Author(s):  
Ming Zhong ◽  
Yulia Komarova ◽  
Jalees Rehman ◽  
Asrar B. Malik
Keyword(s):  
Endothelial Cells ◽  
Critical Role ◽  
Specific Inhibitor ◽  
Tissue Homeostasis ◽  
Cyclic Stretch ◽  
Cardiovascular Development ◽  
Mechanical Stimuli ◽  
Pulmonary Hemodynamics ◽  
Adult Mice ◽  
Piezo Channels

Piezo channels are deemed to constitute one of the most important family of mechanosensing ion channels since their discovery in 2010. With recent advances in identifying their topological structure and the discovery of the agonist Yoda1 as well as the specific inhibitor GsMTx4, it is now possible to study the mechanisms by which Piezo channels are involved in physiological and pathophysiological processes. During embryonic cardiovascular development, Piezo1 senses shear stress and promotes vasculature growth. In adult mice, Piezo1 mediates the release of nitric oxide and ATP from endothelial cells to regulate blood pressure. Piezo channels also play a crucial role in cell differentiation and tissue homeostasis by exquisite mechanical force sensing. Piezo channels are also abundantly expressed in lung tissues. As the lung is exposed to complex pulmonary hemodynamics and respiratory mechanics, cells in the lung, such as microvascular endothelial cells, bear mechanical forces from blood flow shear, pulsatile strain, static pressure, and cyclic stretch due to respiratory movement. These mechanical stimuli are involved in a serial of physiological function and pathophysiological processes of the lung, many of which Piezo channels may be the key player. Mutation of genes encoding Piezo channels are also associated with hereditary human diseases, thus highlighting the critical role of Piezo channels in both tissue homeostasis and disease.

Abstract 278: Cardiac Med1 is Necessary for Postnatal Survival in Mice

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Kathryn M Spitler ◽  
Jessica M Ponce ◽  
Duane D Hall ◽  
Chad E Grueter
Keyword(s):  
Cardiovascular Disease ◽  
Cardiac Function ◽  
Gene Transcription ◽  
Cardiac Development ◽  
Critical Role ◽  
Cardiac Contractility ◽  
Mediator Complex ◽  
Cardiomyocyte Hypertrophy ◽  
And Function

Alterations in gene transcription are commonly associated with cardiovascular disease pathogenesis characterized by cardiomyocyte hypertrophy. The phenotypic responses result in diminished cardiac contractility, ventricular dilation, fibrosis and ultimately sudden death. The mediator complex is a crucial facilitator of gene transcription; however, few studies have investigated the role of mediator in cardiovascular disease initiation and progression. A key subunit of the Mediator complex, MED1, interacts with nuclear receptors to target gene-specific transcription. To determine the role of MED1 in regulating cardiac function, we generated a heart specific knockout of MED1 (cMED1KO). Postnatal deletion of MED1 in mice results in lethality between 3 to 6 weeks of age. The cMED1KO mice display a marked increase in heart mass compared to floxed controls. Furthermore, echocardiography and histological analysis of hearts taken at 3 weeks showed that the cMED1KO animals had decreased cardiac function, increased fibrosis and a dilated left ventricle. Transcriptional changes were observed for key markers of cardiac disease including MYH7, ANF, ACTIN1. We performed RNAseq analysis to identify changes in the transciptome between cMED1KO and floxed control hearts. The analysis unveiled changes in expression of genes regulating cardiac development, metabolism and function. Taken together these results reveal a critical role for MED1 in postnatal cardiac growth and development due to altered gene expression in adult cardiomyocytes.

scholarly journals Small RNA-Sequencing: Approaches and Considerations for miRNA Analysis

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 964
Author(s):  
Sarka Benesova ◽  
Mikael Kubista ◽  
Lukas Valihrach
Keyword(s):  
Rna Sequencing ◽  
Small Rna ◽  
High Sensitivity ◽  
Small Rna Sequencing ◽  
Rna Seq ◽  
Liquid Biopsies ◽  
Comprehensive Overview ◽  
Rna Molecules ◽  
Novel Mirna ◽  
The Many

MicroRNAs (miRNAs) are a class of small RNA molecules that have an important regulatory role in multiple physiological and pathological processes. Their disease-specific profiles and presence in biofluids are properties that enable miRNAs to be employed as non-invasive biomarkers. In the past decades, several methods have been developed for miRNA analysis, including small RNA sequencing (RNA-seq). Small RNA-seq enables genome-wide profiling and analysis of known, as well as novel, miRNA variants. Moreover, its high sensitivity allows for profiling of low input samples such as liquid biopsies, which have now found applications in diagnostics and prognostics. Still, due to technical bias and the limited ability to capture the true miRNA representation, its potential remains unfulfilled. The introduction of many new small RNA-seq approaches that tried to minimize this bias, has led to the existence of the many small RNA-seq protocols seen today. Here, we review all current approaches to cDNA library construction used during the small RNA-seq workflow, with particular focus on their implementation in commercially available protocols. We provide an overview of each protocol and discuss their applicability. We also review recent benchmarking studies comparing each protocol’s performance and summarize the major conclusions that can be gathered from their usage. The result documents variable performance of the protocols and highlights their different applications in miRNA research. Taken together, our review provides a comprehensive overview of all the current small RNA-seq approaches, summarizes their strengths and weaknesses, and provides guidelines for their applications in miRNA research.

scholarly journals Infant circulating MicroRNAs as biomarkers of effect in fetal alcohol spectrum disorders

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amanda H. Mahnke ◽  
Georgios D. Sideridis ◽  
Nihal A. Salem ◽  
Alexander M. Tseng ◽  
R. Colin Carter ◽  
...  
Keyword(s):  
Fetal Alcohol Spectrum Disorders ◽  
Cardiac Development ◽  
Prenatal Alcohol Exposure ◽  
Skeletal Development ◽  
Somatic Growth ◽  
Alcohol Exposure ◽  
Cardiovascular Development ◽  
Relevant Effect ◽  
Cell Cycle Inhibition ◽  
Neurobehavioral Deficits

AbstractPrenatal alcohol exposure (PAE) can result in cognitive and behavioral disabilities and growth deficits. Because alcohol-related neurobehavioral deficits may occur in the absence of overt dysmorphic features or growth deficits, there is a need to identify biomarkers of PAE that can predict neurobehavioral impairment. In this study, we assessed infant plasma extracellular, circulating miRNAs (exmiRNAs) obtained from a heavily exposed Cape Town cohort to determine whether these can be used to predict PAE-related growth restriction and cognitive impairment. PAE, controlling for smoking as a covariate, altered 27% of expressed exmiRNAs with clinically-relevant effect sizes (Cohen’s d ≥ 0.4). Moreover, at 2 weeks, PAE increased correlated expression of exmiRNAs across chromosomes, suggesting potential co-regulation. In confirmatory factor analysis, the variance in expression for PAE-altered exmiRNAs at 2 weeks and 6.5 months was best described by three-factor models. Pathway analysis found that factors at 2 weeks were associated with (F1) cell maturation, cell cycle inhibition, and somatic growth, (F2) cell survival, apoptosis, cardiac development, and metabolism, and (F3) cell proliferation, skeletal development, hematopoiesis, and inflammation, and at 6.5 months with (F1) neurodevelopment, neural crest/mesoderm-derivative development and growth, (F2) immune system and inflammation, and (F3) somatic growth and cardiovascular development. Factors F3 at 2 weeks and F2 at 6.5 months partially mediated PAE-induced growth deficits, and factor F3 at 2 weeks partially mediated effects of PAE on infant recognition memory at 6.5 months. These findings indicate that infant exmiRNAs can help identify infants who will exhibit PAE-related deficits in growth and cognition.

Abstract 791: A Critical Role for Bmper (BMP-binding Endothelial cell precursor-derived Regulator) in Cardiac Muscle Mass Regulation during Development and Pressure Overload Induced Hypertrophy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Monte Willis ◽  
Rongqin Ren ◽  
Cam Patterson
Keyword(s):  
Cardiac Function ◽  
Cardiac Muscle ◽  
Muscle Mass ◽  
Cardiac Development ◽  
Critical Role ◽  
Pressure Overload ◽  
Posterior Wall ◽  
Fractional Shortening

Bone morphogenetic proteins (BMPs) of the TGF-beta superfamily, have been implicated in multiple processes during cardiac development. Our laboratory recently described an unprecedented role for Bmper in antagonizing BMP-2, BMP-4, and BMP-6. To determine the role of Bmper on cardiac development in vivo, we created Bmper null (Bmper −/−) mice by replacing exons 1 and 2 with GFP. Since Bmper −/− mice are perinatally lethal, we determined pre-natal cardiac function of Bmper −/− mice in utero just before birth. By echocardiography, E18.5 Bmper −/− embryos had decreased cardiac function (24.2 +/− 8.1% fractional shortening) compared to Bmper +/− and Bmper +/+ siblings (52.2 +/− 1.6% fractional shortening) (N=4/group). To further characterize the role of Bmper on cardiac function in adult mice, we performed echocardiography on 8-week old male and female Bmper +/− and littermate control Bmper +/+. Bmper +/− mice had an approximately 15% decrease in anterior and posterior wall thickness compared to sibling Bmper +/+ mice at baseline (n=10/group). Cross-sectional areas of Bmper +/− cardiomyocytes were approximately 20% less than wild type controls, indicating cardiomyocyte hypoplasia in adult Bmper +/− mice at baseline. Histologically, no significant differences were identified in representative H&E and trichrome stained adult Bmper +/− and Bmper +/+ cardiac sections at baseline. To determine the effects of Bmper expression on the development of cardiac hypertrophy, both Bmper +/− and Bmper +/+ sibling controls underwent transaortic constriction (TAC), followed by weekly echocardiography. While a deficit was identified in Bmper +/− mice at baseline, both anterior and posterior wall thicknesses increased after TAC, such that identical wall thicknesses were identified in Bmper +/− and Bmper +/+ mice 1–4 weeks after TAC. Notably, cardiac function (fractional shortening %) and histological evaluation revealed no differences between Bmper +/− and Bmper +/+ any time after TAC. These studies identify for the first time that Bmper expression plays a critical role in regulating cardiac muscle mass during development, and that Bmper regulates the development of hypertrophy in response to pressure overload in vivo.

scholarly journals The emerging role of RNAs in DNA damage repair

2017 ◽  
Vol 24 (4) ◽  
pp. 580-587 ◽  
Author(s):  
Ben R Hawley ◽  
Wei-Ting Lu ◽  
Ania Wilczynska ◽  
Martin Bushell
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Critical Role ◽  
Repair Process ◽  
Rna Molecules ◽  
Processing Enzymes ◽  
Damage Repair ◽  
New Findings ◽  
Integral Role ◽  
Repair Mechanisms

Abstract Many surveillance and repair mechanisms exist to maintain the integrity of our genome. All of the pathways described to date are controlled exclusively by proteins, which through their enzymatic activities identify breaks, propagate the damage signal, recruit further protein factors and ultimately resolve the break with little to no loss of genetic information. RNA is known to have an integral role in many cellular pathways, but, until very recently, was not considered to take part in the DNA repair process. Several reports demonstrated a conserved critical role for RNA-processing enzymes and RNA molecules in DNA repair, but the biogenesis of these damage-related RNAs and their mechanisms of action remain unknown. We will explore how these new findings challenge the idea of proteins being the sole participants in the response to DNA damage and reveal a new and exciting aspect of both DNA repair and RNA biology.

scholarly journals Applications of miRNAs in cardiac development, disease progression and regeneration

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jeremy Kah Sheng Pang ◽  
Qian Hua Phua ◽  
Boon-Seng Soh
Keyword(s):  
Cardiac Development ◽  
Control Cell ◽  
Proliferative Potential ◽  
Heart Cells ◽  
Cardiovascular Development ◽  
Developmental Defects ◽  
Protein Coding ◽  
Cardiac Progenitors ◽  
Multiple Levels ◽  
Cell Niche

AbstractDevelopment of the complex human heart is tightly regulated at multiple levels, maintaining multipotency and proliferative state in the embryonic cardiovascular progenitors and thereafter suppressing progenitor characteristics to allow for terminal differentiation and maturation. Small regulatory microRNAs (miRNAs) are at the level of post-transcriptional gene suppressors, which enhance the degradation or decay of their target protein-coding mRNAs. These miRNAs are known to play roles in a large number of biological events, cardiovascular development being no exception. A number of critical cardiac-specific miRNAs have been identified, of which structural developmental defects have been linked to dysregulation of miRNAs in the proliferating cardiac stem cells. These miRNAs present in the stem cell niche are lost when the cardiac progenitors terminally differentiate, resulting in the postnatal mitotic arrest of the heart. Therapeutic applications of these miRNAs extend to the realm of heart failure, whereby the death of heart cells in the ageing heart cannot be replaced due to the arrest of cell division. By utilizing miRNA therapy to control cell cycling, the regenerative potential of matured myocardium can be restored. This review will address the various cardiac progenitor-related miRNAs that control the development and proliferative potential of the heart.

scholarly journals Sequencing of small RNAs of the fern Pleopeltis minima (Polypodiaceae) offers insight into the evolution of the microRNA repertoire in land plants

2016 ◽  
Author(s):  
Florencia Berruezo ◽  
Flavio S. J. de Souza ◽  
Pablo I. Picca ◽  
Sergio I. Nemirovsky ◽  
Leandro Martinez-Tosar ◽  
...  
Keyword(s):  
Small Rna ◽  
Land Plant ◽  
Land Plants ◽  
Phylogenetic Position ◽  
Seed Plants ◽  
Messenger Rnas ◽  
Rna Molecules ◽  
Functional Studies ◽  
Mirna Genes ◽  
Ecological Importance

AbstractMicroRNAs (miRNAs) are short, single stranded RNA molecules that regulate the stability and translation of messenger RNAs in diverse eukaryotic groups. Several miRNA genes are of ancient origin and have been maintained in the genomes of animal and plant taxa for hundreds of millions of years, and functional studies indicate that ancient miRNAs play key roles in development and physiology. In the last decade, genome and small RNA (sRNA) sequencing of several plant species have helped unveil the evolutionary history of land plant miRNAs. Land plants are divided into bryophytes (liverworts, mosses), lycopods (clubmosses and spikemosses), monilophytes (ferns and horsetails), gymnosperms (cycads, conifers and allies) and angiosperms (flowering plants). Among these, the fern group occupies a key phylogenetic position, since it represents the closest extant cousin taxon of seed plants, i.e. gymno- and angiosperms. However, in spite of their evolutionary, economic and ecological importance, no fern genome has been sequenced yet and few genomic resources are available for this group. Here, we sequenced the small RNA fraction of an epiphytic South American fern, Pleopeltis minima (Polypodiaceae), and compared it to plant miRNA databases, allowing for the identification of miRNA families that are shared by all land plants, shared by all vascular plants (tracheophytes) or shared by euphyllophytes (ferns and seed plants) only. Using the recently described transcriptome of another fern, Lygodium japonicum, we also estimated the degree of conservation of fern miRNA targets in relation to other plant groups. Our results pinpoint the origin of several miRNA families in the land plant evolutionary tree with more precision and are a resource for future genomic and functional studies of fern miRNAs.

scholarly journals Histone H1 prevents non-CG methylation-mediated small RNA biogenesis in Arabidopsis heterochromatin

2021 ◽  
Author(s):  
Jaemyung Choi ◽  
David Bruce Lyons ◽  
Daniel Zilberman
Keyword(s):  
Dna Methylation ◽  
Transposable Elements ◽  
Small Rna ◽  
Histone H3 ◽  
Histone H1 ◽  
Dna Methyltransferases ◽  
Flowering Plants ◽  
Genomic Sequences ◽  
Rna Molecules ◽  
Rna Biogenesis

Flowering plants utilize small RNA molecules to guide DNA methyltransferases to genomic sequences. This RNA-directed DNA methylation (RdDM) pathway preferentially targets euchromatic transposable elements. However, RdDM is thought to be recruited by methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin. How RdDM is targeted to euchromatin despite an affinity for H3K9me is unclear. Here we show that loss of histone H1 enhances heterochromatic RdDM, preferentially at nucleosome linker DNA. Surprisingly, this does not require SHH1, the RdDM component that binds H3K9me. Furthermore, H3K9me is dispensable for RdDM, as is CG DNA methylation. Instead, we find that non-CG methylation is specifically required for small RNA biogenesis, and without H1 small RNA production quantitatively expands to non-CG methylated loci. Our results demonstrate that H1 enforces the separation of euchromatic and heterochromatic DNA methylation pathways by excluding the small RNA-generating branch of RdDM from non-CG methylated heterochromatin.

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