Noncoding RNAs implication in cardiovascular diseases in the COVID-19 era

Abstract COronaVIrus Disease 19 (COVID-19) is caused by the infection of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). Although the main clinical manifestations of COVID-19 are respiratory, many patients also display acute myocardial injury and chronic damage to the cardiovascular system. Understanding both direct and indirect damage caused to the heart and the vascular system by SARS-CoV-2 infection is necessary to identify optimal clinical care strategies. The homeostasis of the cardiovascular system requires a tight regulation of the gene expression, which is controlled by multiple types of RNA molecules, including RNA encoding proteins (messenger RNAs) (mRNAs) and those lacking protein-coding potential, the noncoding-RNAs. In the last few years, dysregulation of noncoding-RNAs has emerged as a crucial component in the pathophysiology of virtually all cardiovascular diseases. Here we will discuss the potential role of noncoding RNAs in COVID-19 disease mechanisms and their possible use as biomarkers of clinical use.

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Cell Cycle Control by Nuclear Sequestration ofCDC20andCDH1mRNA in Plant Stem Cells

10.1101/198978 ◽

2017 ◽

Author(s):

Weibing Yang ◽

Raymond Wightman ◽

Elliot M. Meyerowitz

Keyword(s):

Cell Cycle ◽

Nuclear Localization ◽

Cell Cycle Control ◽

Protein Translation ◽

Messenger Rnas ◽

Protein Coding ◽

Rna Molecules ◽

Nuclear Envelope Breakdown ◽

And Function ◽

Necessary And Sufficient

AbstractIn eukaryotic cells, most RNA molecules are exported into the cytoplasm after being transcribed in the nucleus. Long noncoding RNAs (lncRNAs) have been found to reside and function primarily inside the nucleus, but nuclear localization of protein-coding messenger RNAs (mRNAs) has been considered rare in both animals and plants. Here we show that two mRNAs, transcribed from theCDC20andCCS52B(plant orthologue ofCDH1) genes, are specifically sequestered inside the nucleus during the cell cycle. CDC20 and CDH1 both function as coactivators of the anaphase-promoting complex or cyclosome (APC/C) E3 ligase to trigger cyclin B (C YCB) destruction. In theArabidopsis thalianashoot apical meristem (SAM), we findCDC20andCCS52Bare co-expressed withCYCBsin mitotic cells.CYCBtranscripts can be exported and translated, whereasCDC20andCCS52BmRNAs are strictly confined to the nucleus at prophase and the cognate proteins are not translated until the redistribution of the mRNAs to the cytoplasm after nuclear envelope breakdown (NEBD) at prometaphase. The 5’ untranslated region (UTR) is necessary and sufficient forCDC20mRNA nuclear localization as well as protein translation. Mitotic enrichment ofCDC20andCCS52Btranscripts enables the timely and rapid activation of APC/C, while their nuclear sequestration at prophase appears to protect cyclins from precocious degradation.

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The Role of MicroRNA and LncRNA–MicroRNA Interactions in Regulating Ischemic Heart Disease

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248416667600 ◽

2016 ◽

Vol 22 (2) ◽

pp. 105-111 ◽

Cited By ~ 18

Author(s):

Na Li ◽

Murugavel Ponnusamy ◽

Meng-peng Li ◽

Kun Wang ◽

Pei-Feng Li

Keyword(s):

Heart Disease ◽

Ischemic Heart Disease ◽

Heart Diseases ◽

Noncoding Rnas ◽

Ischemic Heart ◽

Messenger Rnas ◽

Protein Coding ◽

Coding Regions ◽

Pathological Cardiac Hypertrophy

Approximately 2% of the human genome consists of protein-coding regions. Therefore, the majority of transcripts are noncoding RNAs, such as microRNA (miRNA) and long noncoding RNAs (lncRNAs). In ischemic heart disease, the majority of miRNAs are repressors or destabilizers of target messenger RNAs. The lncRNAs are a second class of noncoding RNAs that have recently gained attention for their roles in heart disease and in regulating the functions of miRNA. In this review, we summarize the role of miRNA in pathological cardiac hypertrophy and myocardial infarction. In addition, we discuss the functional interactions of miRNA and lncRNA and its impact on these ischemic heart diseases.

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Cellular RNA surveillance in health and disease

Science ◽

10.1126/science.aax2957 ◽

2019 ◽

Vol 366 (6467) ◽

pp. 822-827 ◽

Cited By ~ 18

Author(s):

Sandra L. Wolin ◽

Lynne E. Maquat

Keyword(s):

Quality Control ◽

Noncoding Rnas ◽

Messenger Rnas ◽

Interferon Production ◽

Developmental Defects ◽

Protein Coding ◽

Ribonucleic Acids ◽

Rna Surveillance ◽

Health And Disease

The numerous quality control pathways that target defective ribonucleic acids (RNAs) for degradation play key roles in shaping mammalian transcriptomes and preventing disease. These pathways monitor most steps in the biogenesis of both noncoding RNAs (ncRNAs) and protein-coding messenger RNAs (mRNAs), degrading ncRNAs that fail to form functional complexes with one or more proteins and eliminating mRNAs that encode abnormal, potentially toxic proteins. Mutations in components of diverse RNA surveillance pathways manifest as disease. Some mutations are characterized by increased interferon production, suggesting that a major role of these pathways is to prevent aberrant cellular RNAs from being recognized as “non-self.” Other mutations are common in cancer, or result in developmental defects, revealing the importance of RNA surveillance to cell and organismal function.

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SARS-CoV-2, Cardiovascular Diseases and Noncoding RNAs: A Connected Triad

International Journal of Molecular Sciences ◽

10.3390/ijms222212243 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12243

Author(s):

Lucia Natarelli ◽

Fabio Virgili ◽

Christian Weber

Keyword(s):

Gene Expression ◽

Cardiovascular Diseases ◽

Regulation Of Gene Expression ◽

Noncoding Rnas ◽

Adverse Outcomes ◽

Rna Molecules ◽

Clinical Level ◽

Important Target ◽

Stable Conditions

Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is characterized by important respiratory impairments frequently associated with severe cardiovascular damages. Moreover, patients with pre-existing comorbidity for cardiovascular diseases (CVD) often present a dramatic increase in inflammatory cytokines release, which increases the severity and adverse outcomes of the infection and, finally, mortality risk. Despite this evident association at the clinical level, the mechanisms linking CVD and COVID-19 are still blurry and unresolved. Noncoding RNAs (ncRNAs) are functional RNA molecules transcribed from DNA but usually not translated into proteins. They play an important role in the regulation of gene expression, either in relatively stable conditions or as a response to different stimuli, including viral infection, and are therefore considered a possible important target in the design of specific drugs. In this review, we introduce known associations and interactions between COVID-19 and CVD, discussing the role of ncRNAs within SARS-CoV-2 infection from the perspective of the development of efficient pharmacological tools to treat COVID-19 patients and taking into account the equally dramatic associated consequences, such as those affecting the cardiovascular system.

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Application of Long Noncoding RNAs in Osteosarcoma: Biomarkers and Therapeutic Targets

Cellular Physiology and Biochemistry ◽

10.1159/000479205 ◽

2017 ◽

Vol 42 (4) ◽

pp. 1407-1419 ◽

Cited By ~ 72

Author(s):

Zhihong Li ◽

Pengcheng Dou ◽

Tang Liu ◽

Shasha He

Keyword(s):

Prognostic Biomarker ◽

Noncoding Rnas ◽

Therapeutic Targets ◽

Therapeutic Strategies ◽

Long Noncoding Rnas ◽

Protein Coding ◽

Rna Molecules ◽

Primary Bone ◽

Coding Potential ◽

Potential Biomarkers

Osteosarcoma is the most common primary bone malignancy in children and adolescents. Although improvements in therapeutic strategies were achieved, the outcome remains poor for most patients with metastatic or recurrent osteosarcoma. Therefore, it is imperative to identify novel and effective prognostic biomarker and therapeutic targets for the disease. Long noncoding RNAs (lncRNAs) are a novel class of RNA molecules defined as transcripts >200 nucleotides that lack protein coding potential. Many lncRNAs are deregulated in cancer and are important regulators for malignancies. Nine lncRNAs (91H, BCAR4, FGFR3-AS1, HIF2PUT, HOTTIP, HULC, MALAT-1, TUG1, UCA1) are upregulated and considered oncogenic for osteosarcoma. Loc285194 and MEG3 are two lncRNAs downregulated and as tumor suppressor for the disease. Moreover, the expressions of LINC00161 and ODRUL are associated with chemo-resistance of osteosarcoma. The mechanisms for these lncRNAs in regulating development of osteosarcoma are diverse, e.g. ceRNA, Wnt/β-catenin pathway, etc. The lncRNAs identified may serve as potential biomarkers or therapeutic targets for osteosarcoma.

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NOVOMIR: De Novo Prediction of MicroRNA-Coding Regions in a Single Plant-Genome

Journal of Nucleic Acids ◽

10.4061/2010/495904 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 25

Author(s):

Jan-Hendrik Teune ◽

Gerhard Steger

Keyword(s):

Noncoding Rna ◽

De Novo ◽

Plant Genome ◽

Messenger Rnas ◽

Protein Coding ◽

Rna Molecules ◽

Coding Regions ◽

Mirna Genes ◽

Genomic Scale ◽

Eukaryotic Genomes

MicroRNAs (miRNA) are small regulatory, noncoding RNA molecules that are transcribed as primary miRNAs (pri-miRNA) from eukaryotic genomes. At least in plants, their regulatory activity is mediated through base-pairing with protein-coding messenger RNAs (mRNA) followed by mRNA degradation or translation repression. We describeNOVOMIR, a program for the identification of miRNA genes in plant genomes. It uses a series of filter steps and a statistical model to discriminate a pre-miRNA from other RNAs and does rely neither on prior knowledge of a miRNA target nor on comparative genomics. The sensitivity and specificity ofNOVOMIR for detection of premiRNAs fromArabidopsis thalianais ~0.83 and ~0.99, respectively. Plant pre-miRNAs are more heterogeneous with respect to size and structure than animal pre-miRNAs. Despite these difficulties,NOVOMIR is well suited to perform searches for pre-miRNAs on a genomic scale.NOVOMIR is written in Perl and relies on two additional, free programs for prediction of RNA secondary structure (RNALFOLD, RNASHAPES).

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Non-Coding RNA Databases in Cardiovascular Research

Non-Coding RNA ◽

10.3390/ncrna6030035 ◽

2020 ◽

Vol 6 (3) ◽

pp. 35

Author(s):

Deepak Balamurali ◽

Monika Stoll

Keyword(s):

Vascular System ◽

Cardiovascular Research ◽

Data Repositories ◽

Protein Coding ◽

Rna Molecules ◽

High Throughput Data ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Generation Sequencing

Cardiovascular diseases (CVDs) are of multifactorial origin and can be attributed to several genetic and environmental components. CVDs are the leading cause of mortality worldwide and they primarily damage the heart and the vascular system. Non-coding RNA (ncRNA) refers to functional RNA molecules, which have been transcribed into DNA but do not further get translated into proteins. Recent transcriptomic studies have identified the presence of thousands of ncRNA molecules across species. In humans, less than 2% of the total genome represents the protein-coding genes. While the role of many ncRNAs is yet to be ascertained, some long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been associated with disease progression, serving as useful diagnostic and prognostic biomarkers. A plethora of data repositories specialized in ncRNAs have been developed over the years using publicly available high-throughput data from next-generation sequencing and other approaches, that cover various facets of ncRNA research like basic and functional annotation, expressional profile, structural and molecular changes, and interaction with other biomolecules. Here, we provide a compendium of the current ncRNA databases relevant to cardiovascular research.

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Genome-Wide Identification of Barley Long Noncoding RNAs and Analysis of Their Regulatory Interactions during Shoot and Grain Development

International Journal of Molecular Sciences ◽

10.3390/ijms22105087 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5087

Author(s):

Sebastian Gasparis ◽

Mateusz Przyborowski ◽

Anna Nadolska-Orczyk

Keyword(s):

Target Genes ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Shoot Apices ◽

Protein Coding ◽

Cis Acting ◽

Rna Molecules ◽

Functional Studies ◽

Potential Target ◽

Genome Wide

Long noncoding RNAs (lncRNAs) are a class of RNA molecules with gene regulatory functions in plant development and the stress response. Although the number of lncRNAs identified in plants is rapidly increasing, very little is known about their role in barley development. In this study, we performed global identification of barley lncRNAs based on 53 RNAseq libraries derived from nine different barley tissues and organs. In total, 17,250 lncRNAs derived from 10,883 loci were identified, including 8954 novel lncRNAs. Differential expression of lncRNAs was observed in the developing shoot apices and grains, the two organs that have a direct influence on the final yield. The regulatory interaction of differentially expressed lncRNAs with the potential target genes was evaluated. We identified 176 cis-acting lncRNAs in shoot apices and 424 in grains, while the number of trans-acting lncRNAs in these organs was 1736 and 540, respectively. The potential target protein-coding genes were identified, and their biological function was annotated using MapMan ontology. This is the first insight into the roles of lncRNAs in barley development on the genome-wide scale, and our results provide a solid background for future functional studies.

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COVID-19 and cardiovascular diseases

Journal of Molecular Cell Biology ◽

10.1093/jmcb/mjaa064 ◽

2020 ◽

Author(s):

Fan Liu ◽

Feng Liu ◽

Lu Wang

Keyword(s):

Cardiovascular Diseases ◽

Cardiovascular System ◽

Vascular System ◽

Public Health Emergency ◽

Global Public Health ◽

Angiotensin Converting Enzyme 2 ◽

Clinical Complications ◽

Clinical Observations ◽

Underlying Mechanisms ◽

Experimental Findings

Abstract The coronavirus disease 2019 (COVID-19) remains a global public health emergency. Despite being caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), besides the lung, this infectious disease also has severe implications in cardiovascular system. In this review, we summarize diverse clinical complications of heart and vascular system, as well as the relevant high mortality, in COVID-19 patients. Systemic inflammation and angiotensin-converting enzyme 2-involved signaling networking in SARS-CoV-2 infection and cardiovascular system may contribute to the manifestations of cardiovascular diseases. Therefore, integration of clinical observations and experimental findings can promote our understanding of the underlying mechanisms, which would aid in identifying and treating the cardiovascular injury in patients with COVID-19 appropriately.

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Regulatory RNAs in Heart Failure

Circulation ◽

10.1161/circulationaha.119.042474 ◽

2020 ◽

Vol 141 (4) ◽

pp. 313-328 ◽

Cited By ~ 16

Author(s):

Clarissa Pedrosa da Costa Gomes ◽

Blanche Schroen ◽

Gabriela M. Kuster ◽

Emma L. Robinson ◽

Kerrie Ford ◽

...

Keyword(s):

Gene Expression ◽

Heart Failure ◽

Cardiovascular Disease ◽

Noncoding Rna ◽

Regulation Of Gene Expression ◽

Noncoding Rnas ◽

Circular Rnas ◽

Regulatory Rna ◽

Messenger Rnas ◽

Protein Coding

Cardiovascular disease is an enormous socioeconomic burden worldwide and remains a leading cause of mortality and disability despite significant efforts to improve treatments and personalize healthcare. Heart failure is the main manifestation of cardiovascular disease and has reached epidemic proportions. Heart failure follows a loss of cardiac homeostasis, which relies on a tight regulation of gene expression. This regulation is under the control of multiple types of RNA molecules, some encoding proteins (the so-called messenger RNAs) and others lacking protein-coding potential, named noncoding RNAs. In this review article, we aim to revisit the notion of regulatory RNA, which has been thus far mainly confined to noncoding RNA. Regulatory RNA, which we propose to abbreviate as regRNA, can include both protein-coding RNAs and noncoding RNAs, as long as they contribute, directly or indirectly, to the regulation of gene expression. We will address the regulation and functional role of messenger RNAs, microRNAs, long noncoding RNAs, and circular RNAs (ie, regRNAs) in heart failure. We will debate the utility of regRNAs to diagnose, prognosticate, and treat heart failure, and we will provide directions for future work.

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