MicroRNAs: From Junk RNA to Life Regulators and Their Role in Cardiovascular Disease

MicroRNAs (miRNAs) are single-stranded small non-coding RNA (18–25 nucleotides) that until a few years ago were considered junk RNA. In the last twenty years, they have acquired more importance thanks to the understanding of their influence on gene expression and their role as negative regulators at post-transcriptional level, influencing the stability of messenger RNA (mRNA). Approximately 5% of the genome encodes miRNAs which are responsible for regulating numerous signaling pathways, cellular processes and cell-to-cell communication. In the cardiovascular system, miRNAs control the functions of various cells, such as cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts, playing a role in physiological and pathological processes and seeming also related to variations in contractility and hereditary cardiomyopathies. They provide a new perspective on the pathophysiology of disorders such as hypertrophy, fibrosis, arrhythmia, inflammation and atherosclerosis. MiRNAs are differentially expressed in diseased tissue and can be released into the circulation and then detected. MiRNAs have become interesting for the development of new diagnostic and therapeutic tools for various diseases, including heart disease. In this review, the concept of miRNAs and their role in cardiomyopathies will be introduced, focusing on their potential as therapeutic and diagnostic targets (as biomarkers).

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The role of vitamins and minerals in modulating the expression of microRNA

Nutrition Research Reviews ◽

10.1017/s0954422414000043 ◽

2014 ◽

Vol 27 (1) ◽

pp. 94-106 ◽

Cited By ~ 23

Author(s):

Emma L. Beckett ◽

Zoe Yates ◽

Martin Veysey ◽

Konsta Duesing ◽

Mark Lucock

Keyword(s):

Gene Expression ◽

Food Sources ◽

Transcriptional Level ◽

Disease States ◽

Regulatory Circuit ◽

Non Coding Rna ◽

Epigenetic Machinery ◽

Health And Disease ◽

Expression Potential

A growing number of studies in recent years have highlighted the importance of molecular nutrition as a potential determinant of health and disease. In particular, the ability of micronutrients to regulate the final expression of gene products via modulation of transcription and translation is now being recognised. Modulation of microRNA (miRNA) by nutrients is one pathway by which nutrition may mediate gene expression. miRNA, a class of non-coding RNA, can directly regulate gene expression post-transcriptionally. In addition, miRNA are able to indirectly influence gene expression potential at the transcriptional level via modulation of the function of components of the epigenetic machinery (DNA methylation and histone modifications). These mechanisms interact to form a complex, bi-directional regulatory circuit modulating gene expression. Disease-specific miRNA profiles have been identified in multiple disease states, including those with known dietary risk factors. Therefore, the role that nutritional components, in particular, vitamins and minerals, play in the modulation of miRNA profiles, and consequently health and disease, is increasingly being investigated, and as such is a timely subject for review. The recently posited potential for viable exogenous miRNA to enter human blood circulation from food sources adds another interesting dimension to the potential for dietary miRNA to contribute to gene modulation.

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MicroRNA-mediated gene silencing: are we close to a unifying model?

BioMolecular Concepts ◽

10.1515/bmc.2011.047 ◽

2012 ◽

Vol 3 (1) ◽

pp. 29-40 ◽

Cited By ~ 2

Author(s):

Victoria James ◽

Sybil C.K. Wong ◽

Tyson V. Sharp

Keyword(s):

Gene Expression ◽

Gene Silencing ◽

Messenger Rna ◽

Transcriptional Regulators ◽

Effector Proteins ◽

Specific Reference ◽

Functional Studies ◽

Non Coding Rna ◽

Almost All ◽

Terminal Effector

AbstractMicroRNAs (miRNAs) comprise a group of small non-coding RNA –21 nucleotides in length. They act as post-transcriptional regulators of gene expression by forming base pairing interactions with target messenger RNA (mRNA). At least 1000 miRNAs are predicted to be expressed in humans and are encoded for in the genome of almost all organisms. Functional studies indicate that every cellular process studied thus far is regulated at some level by miRNAs. Given this expansive role, it is not surprising that disruption of this crucial pathway underlies the initiation of, or in the least, contributes to the development and progression of numerous human diseases and physiological disorders. This review will focus on the latest developments in uncovering the mechanism(s) of miRNA-mediated silencing with specific reference to the function of terminal effector proteins, how translation of target mRNA is inhibited and whether we are moving towards understanding this fundamental gene silencing paradigm.

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Bio Immune(G)ene Medicine and the Use of miRNAs to Regulate the Cell

Advances in Bioengineering and Biomedical Science Research ◽

10.33140/abbsr/01/02/00001 ◽

2018 ◽

Vol 1 (2) ◽

Keyword(s):

Gene Expression ◽

Target Genes ◽

Allergic Diseases ◽

Degradation Process ◽

Transcriptional Level ◽

Collateral Damage ◽

Rna Molecules ◽

The Past ◽

Needed Information ◽

Non Coding Rna

MicroRNAs (miRNAs or miRs) are a type of non-coding RNA molecules that regulate the gene expression in a negative way, by downregulating the gene expression mainly at the post-transcriptional level, either by the mRNA degradation process or the inhibition of the translation. The role that many miRNAs play in the pathogenesis of several diseases is well known, such as in the inflammation process, in several steps of the oncogenesis or the metabolism of several virus and bacteria among many others. One of the main limitations in the therapeutic use of miRNAs is the ability to reach the target, as well as doing so without causing any collateral damage. One microRNA can indeed regulate up to 200 target-genes, and one gene can be influenced by a lot of different microRNAs. This is the purpose of the Bio Immune(G)ene Medicine: to achieve the cell without harm, use all the molecular resources available, especially epigenetic with the microRNAs, and to restore the cell homeostasis. The Bio Immune(G)ene Medicine only seeks to play a regulatory biomimetic role, to give the cell the needed information for its own right regulation. Our experience in cell regulation for the past few years has shown the way to fight, for instance, against the deleterious effects of viruses or bacteria in the lymphocytes, also at the background of many autoimmune or allergic diseases, as well as to regulate many other pathological processes. To fulfil this purpose, nanobiotechnology is used to reach the targets; we thus introduce very low doses of miRNAs in nano compounds with the aim to promote the regulation of the main signalling pathways disturbed in a given pathology.

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How long does the mRNA remains stable in untreated whole bovine blood?

10.21203/rs.3.rs-434702/v2 ◽

2021 ◽

Author(s):

Rodrigo Giglioti ◽

Bianca Tainá Azevedo ◽

Henrique Nunes de Oliveira ◽

Luciana Morita Katiki ◽

Anibal Eugênio Vercesi Filho ◽

...

Keyword(s):

Gene Expression ◽

Messenger Rna ◽

Expression Patterns ◽

Rna Extraction ◽

Bovine Blood ◽

Rna Integrity ◽

Expression Studies ◽

Gene Expression Studies ◽

Altered Gene ◽

The Stability

Abstract Background: High quality and quantity of messenger RNA (mRNA) are required for accuracy of gene expression studies and other RNA-based downstream applications. Since RNA is considered a labile macromolecular prone to degradation, which may result in falsely altered gene expression patterns, several commercial stabilizing reagents have been developed aiming to keep RNA stable for long period. However, for studies involving large number of experimental samples, the high costs related to these specific reagents may constitute a barrier. Methods and Results: In this context the present study was designed aiming to evaluate the stability of mRNA in whole bovine blood collected in EDTA tubes during storage at common fridge (4°C). Whole blood samples were collected from six Holstein calves and submitted to RNA extraction in each different interval: immediately after blood sampling (< 2 h), at 1-day post-sampling (dps), 2 dps, 3 dps, 7 dps and 14dps intervals. RNA integrity and purity were evaluated, and RT-qPCR assays were run using seven different genes (B2M, ACTB, PPIA, GAPDH, YWHAZ, CD4 and IFN-γ) aiming to evaluate the presence of altered gene transcription during storage. All extracted RNA samples presented high purity, while optimal integrity and unaltered gene expression were observed in whole experimental group up to 3 days of storage.Conclusion: Bovine blood RNA remained stable in K3EDTA tubes for 3 days stored at common fridge and can be successfully and accurately used for gene expression studies.

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MiR-155: An Important Regulator of Neuroinflammation

International Journal of Molecular Sciences ◽

10.3390/ijms23010090 ◽

2021 ◽

Vol 23 (1) ◽

pp. 90

Author(s):

Valeria Domenica Zingale ◽

Agnese Gugliandolo ◽

Emanuela Mazzon

Keyword(s):

Neurological Diseases ◽

Transcriptional Level ◽

Regulate Gene Expression ◽

Rna Molecules ◽

Cellular Processes ◽

Non Coding Rna ◽

Important Regulator ◽

The Central Nervous System ◽

High Concentrations ◽

Mirnas Expression

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and that play an important role in many cellular processes, including modulation of inflammation. MiRNAs are present in high concentrations in the central nervous system (CNS) and are spatially and temporally expressed in a specific way. Therefore, an imbalance in the expression pattern of these small molecules can be involved in the development of neurological diseases. Generally, CNS responds to damage or disease through the activation of an inflammatory response, but many neurological disorders are characterized by uncontrolled neuroinflammation. Many studies support the involvement of miRNAs in the activation or inhibition of inflammatory signaling and in the promotion of uncontrolled neuroinflammation with pathological consequences. MiR-155 is a pro-inflammatory mediator of the CNS and plays an important regulatory role. The purpose of this review is to summarize how miR-155 is regulated and the pathological consequences of its deregulation during neuroinflammatory disorders, including multiple sclerosis, Alzheimer’s disease and other neuroinflammatory disorders. Modulation of miRNAs’ expression could be used as a therapeutic strategy in the treatment of pathological neuroinflammation.

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Stable reference genes for RT-qPCR analysis of gene expression in the Musa acuminata-Pseudocercospora musae interaction

Scientific Reports ◽

10.1038/s41598-019-51040-z ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Erica Cristina Silva Rego ◽

Tatiana David Miranda Pinheiro ◽

Jose Dijair Antonino ◽

Gabriel Sergio Costa Alves ◽

Michelle Guitton Cotta ◽

...

Keyword(s):

Gene Expression ◽

Reference Genes ◽

Target Genes ◽

Resistance Mechanisms ◽

Musa Acuminata ◽

Limiting Factors ◽

Mrna Levels ◽

Analytical Technique ◽

Cellular Processes ◽

The Stability

Abstract Leaf pathogens are limiting factors in banana (Musa spp.) production, with Pseudocercospora spp. responsible for the important Sigatoka disease complex. In order to investigate cellular processes and genes involved in host defence responses, quantitative real-time PCR (RT-qPCR) is an analytical technique for gene expression quantification. Reliable RT-qPCR data, however, requires that reference genes for normalization of mRNA levels in samples are validated under the conditions employed for expression analysis of target genes. We evaluated the stability of potential reference genes ACT1, α-TUB, UBQ1, UBQ2, GAPDH, EF1α, APT and RAN. Total RNA was extracted from leaf tissues of Musa acuminata genotypes Calcutta 4 (resistant) and Cavendish Grande Naine (susceptible), both subjected to P. musae infection. Expression stability was determined with NormFinder, BestKeeper, geNorm and RefFinder algorithms. UBQ2 and RAN were the most stable across all M. acuminata samples, whereas when considering inoculated and non-inoculated leaf samples, APT and UBQ2 were appropriate for normalization in Calcutta 4, with RAN and α-TUB most stable in Cavendish Grande Naine. This first study of reference genes for relative quantification of target gene expression in the M. acuminata-P. musae interaction will enable reliable analysis of gene expression in this pathosystem, benefiting elucidation of disease resistance mechanisms.

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The G20210A mutation does not affect the stability of prothrombin mRNA in vivo

Blood ◽

10.1182/blood-2002-02-0412 ◽

2002 ◽

Vol 100 (1) ◽

pp. 359-362 ◽

Cited By ~ 34

Author(s):

Eleanor S. Pollak ◽

Ho-Sun Lam ◽

J. Eric Russell

Keyword(s):

Mrna Stability ◽

Messenger Rna ◽

Thrombotic Risk ◽

Cellular Processes ◽

G20210a Mutation ◽

Alternate Model ◽

Prothrombin Gene ◽

The Stability ◽

Prothrombin 20210A

Abstract The activated form of prothrombin plays pivotal roles in the regulation of crucial coagulation, fibrinolytic, and cellular processes. Among several congenital genetic defects affecting the prothrombin gene, a G→A mutation at position 20210—the accepted polyadenylation site—has been linked to hyperprothrombinemia and a corresponding increase in venous and arterial thrombotic risk. The current study substantiates the hypothesis that the 20210A mutation effects posttranscriptional dysregulation of the prothrombin messenger RNA (mRNA). Moreover, data from experiments carried out in fresh liver tissue indicate that the 20210A mutation does not affect prothrombin mRNA stability but, rather, effects a change in the location of the 3′-cleavage/polyadenylation reaction. Based upon this evidence, we propose an alternate model for the dysregulated expression of the prothrombin 20210A gene that does not require a change in the stability of its mRNA.

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Quantifying the noise in bursty gene expression under regulation by small RNAs

International Journal of Modern Physics C ◽

10.1142/s0129183119400023 ◽

2019 ◽

Vol 30 (07) ◽

pp. 1940002

Author(s):

Shigang Qiu ◽

Tao Jia

Keyword(s):

Gene Expression ◽

Protein Level ◽

Small Rnas ◽

Messenger Rna ◽

Living System ◽

Accurate Solution ◽

Gene Expression Noise ◽

Cellular Processes ◽

Post Transcriptional Regulation ◽

Analytical Tools

Gene expression is a fundamental process in a living system. The small RNAs (sRNAs) is widely observed as a global regulator in gene expression. The inherent nonlinearity in this regulatory process together with the bursty production of messenger RNA (mRNA), sRNA and protein make the exact solution for this stochastic process intractable. This is particularly the case when quantifying the protein noise level, which has great impact on multiple cellular processes. Here, we propose an approximate yet reasonably accurate solution for the gene expression noise with infrequent burst and strong regulation by sRNAs. This analytical solution allows us to better analyze the noise and stochastic deviation of protein level. We find that the regulation amplifies the noise, reduces the protein level. The stochasticity in the regulation generates more proteins than what if the stochasticity is removed from the system. The sRNA level is most important to the relationship between the noise and stochastic deviation. The results provide analytical tools for more general studies of gene expression and strengthen our quantitative understandings of post-transcriptional regulation in controlling gene expression processes.

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Validation of reference genes for quantitative RT-PCR normalization inSuaeda aralocaspica, an annual halophyte with heteromorphism and C4 pathway without Kranz anatomy

PeerJ ◽

10.7717/peerj.1697 ◽

2016 ◽

Vol 4 ◽

pp. e1697 ◽

Cited By ~ 11

Author(s):

Jing Cao ◽

Lu Wang ◽

Haiyan Lan

Keyword(s):

Gene Expression ◽

Reference Gene ◽

Reference Genes ◽

Transcriptional Level ◽

28S Rrna ◽

Related Gene ◽

Kranz Anatomy ◽

Qrt Pcr ◽

C4 Pathway ◽

The Stability

Reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) is a powerful analytical technique for the measurement of gene expression, which depends on the stability of the reference gene used for data normalization.Suaeda aralocaspica, an annual halophyte with heteromorphic seeds and possessing C4 photosynthesis pathway without Kranz anatomy, is an ideal plant species to identify stress tolerance-related genes and compare relative expression at transcriptional level. So far, no molecular information is available for this species. In the present study, six traditionally used reference genes were selected and their expression stability in two types of seeds ofS. aralocaspicaunder different experimental conditions was evaluated. Three analytical programs, geNorm, NormFinder and BestKeeper, were used to assess and rank the stability of reference gene expression. Results revealed that although some reference genes may display different transcriptional profiles between the two types of seeds,β-TUB andGAPDHappeared to be the most suitable references under different developmental stages and tissues.GAPDHwas the appropriate reference gene under different germination time points and salt stress conditions, andACTINwas suitable for various abiotic stress treatments for the two types of seeds. For all the sample pools,β-TUB served as the most stable reference gene, whereas18S rRNAand28S rRNAperformed poorly and presented as the least stable genes in our study.UBQseemed to be unsuitable as internal control under different salt treatments. In addition, the expression of a photosynthesis-related gene (PPDK) of C4 pathway and a salt tolerance-related gene (SAT) ofS. aralocaspicawere used to validate the best performance reference genes. This is the first systematic comparison of reference gene selection for qRT-PCR work inS. aralocaspicaand these data will facilitate further studies on gene expression in this species and other euhalophytes.

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Evolutionarily Conserved Long Non-coding RNA Regulates Gene Expression in Cytokine Storm During COVID-19

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2020.582953 ◽

2021 ◽

Vol 8 ◽

Author(s):

Olanrewaju B. Morenikeji ◽

Kahleel Bernard ◽

Ellis Strutton ◽

Madeleine Wallace ◽

Bolaji N. Thomas

Keyword(s):

Gene Expression ◽

Drug Targets ◽

Regulatory Elements ◽

Cytokine Storm ◽

Cellular Processes ◽

Non Coding Rna ◽

Evolutionarily Conserved ◽

Multiple Species

Coronavirus is a family of viruses including alpha-, beta-, gamma-, delta-coronaviruses. Only alpha- and betacoronaviruses have been observed to infect humans. Past outbreaks of SARS-CoV and MERS-CoV, both betacoronavirus, are the result of a spillover from animals. Recently, a new strain termed SARS-CoV-2 emerged in December 2019 in Wuhan, China. Severe cases of COVID-19, the disease caused by SARS-CoV-2, lead to acute respiratory distress syndrome (ARDS). One contributor to the development of ARDS is cytokine storm, an overwhelming inflammatory immune response. Long non-coding RNAs (lncRNAs) are genetic regulatory elements that, among many functions, alter gene expression and cellular processes. lncRNAs identified to be pertinent in COVID-19 cytokine storm have the potential to serve as disease markers or drug targets. This project aims to computationally identify conserved lncRNAs potentially regulating gene expression in cytokine storm during COVID-19. We found 22 lncRNAs that can target 10 cytokines overexpressed in COVID-19 cytokine storm, 8 of which targeted two or more cytokine storm cytokines. In particular, the lncRNA non-coding RNA activated by DNA damage (NORAD), targeted five out of the ten identified cytokine storm cytokines, and is evolutionarily conserved across multiple species. These lncRNAs are ideal candidates for further in vitro and in vivo analysis.

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