scholarly journals Human Genes Are In Silico Potential Targets For Rice miRNA

2020 ◽  
Author(s):  
Aizhan Rakhmetullina ◽  
Anna Pyrkova ◽  
Dana Aisina ◽  
Anatoliy Ivashchenko
Keyword(s):  
Free Energy ◽  
Neurodegenerative Diseases ◽  
Candidate Genes ◽  
Human Body ◽  
Binding Sites ◽  
In Silico ◽  
Target Genes ◽  
A Value ◽  
Human Genes ◽  
Number Of Genes

AbstractExogenous miRNAs enter the human body through food, and their effects on metabolic processes can be considerable. It is important to determine which miRNAs from plants affect the expression of human genes and the extent of their influence. The binding sites of 738 osa-miRNAs that interact with 17508 mRNAs of human genes were determined using the MirTarget program. The characteristics of the binding of 46 single osa-miRNAs to 86 mRNAs of human genes with a value of free energy (ΔG) interaction equal 94% to 100% from maximum ΔG were established. The findings showed that osa-miR2102-5p, osa-miR5075-3p, osa-miR2097-5p, osa-miR2919 targeted the largest number of genes at 38, 36, 23, 19 sites, respectively. mRNAs of 86 human genes were identified as targets for 93 osa-miRNAs of all family osa-miRNAs with ΔG values equal 94% to 98% from maximum ΔG. Each miRNA of the osa-miR156-5p, osa-miR164-5p, osa-miR168-5p, osa-miR395-3p, osa-miR396-3p, osa-miR396-5p, osa-miR444-3p, osa-miR529-3p, osa-miR1846-3p, osa-miR2907-3p families had binding sites in mRNAs of several human target genes. The binding sites of osa-miRNAs in mRNAs of the target genes for each family of osa-miRNAs were conserved when compared to flanking nucleotide sequences. mRNA human genes of osa-miRNAs are candidate genes of cancer, cardiovascular and neurodegenerative diseases.

scholarly journals How miRNAs can protect humans from coronaviruses COVID-19, SARS-CoV, and MERS-CoV

2020 ◽  
Author(s):  
Anatoliy Ivashchenko ◽  
Aizhan Rakhmetullina ◽  
Dana Aisina
Keyword(s):  
Free Energy ◽  
Binding Sites ◽  
Target Genes ◽  
Economic Losses ◽  
Binding Characteristics ◽  
The Past ◽  
A Value ◽  
Energy Interaction ◽  
2D Structure ◽  
Regulate Protein

Abstract Viral diseases cause significant harm to human health and often cause high mortality. In the past twenty years, humanity has undergone infection by SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome) and COVID-19 coronaviruses, which spread from animals to humans and from person to person. These diseases have led to large economic losses. To fight coronaviruses and other viruses, it is proposed to use miRNAs, which regulate protein synthesis at the translational level. MirTarget program was used to determine the following binding characteristics: the locations of miRNA binding sites in the 3'UTR, 5'UTR, and CDS; the free energy interaction ∆G between miRNA and mRNA; the ΔG/ΔGm value, where ΔGm is equal to the free energy binding of miRNA with its full complementary nucleotide sequence; and the nucleotide interaction schemes between miRNAs and mRNAs. Out of 2565 miRNAs, miR-4778-3p, miR-6864-5p and miR-5197-3p were identified as the most effectively interacting with the gRNA of SARS-CoV, MERS-CoV and COVID-19, respectively. Based on the miR-4778-3p, miR-6864-5p and miR-5197-3p sequences, complete complementary miRNA (cc-miR) binding sites in the gRNA coronaviruses were created. The detected binding sites of these cc-miRs did not form intramolecular complexes in the 2D structure of the gRNA of SARS-CoV, MERS-CoV, and COVID-19 with a value of more than 85%. Therefore, the cc-miRs will bind gRNA at these sites without competition. The cc-miRs for SARS-CoV, MERS-CoV, and COVID-19 did not have target genes among the 17508 human coding genes with a ΔG/ΔGm of more than 85%, which implies the absence of side effects of these cc-miRs on the translation of human mRNAs. cc-miRs can be used as therapeutic agents by incorporating them into exosomes or other vesicles and introducing them into the blood or lung by inhalation. The introduction of cc-miR into the blood will suppress the reproduction of the virus in the blood and in all organs into which it can enter. The proposed method of inhibiting the reproduction of coronaviruses can be used for other viruses.

The search of CAR, AhR, ESRs binding sites in promoters of intronic and intergenic microRNAs

2018 ◽  
Vol 16 (01) ◽  
pp. 1750029 ◽  
Author(s):  
Vladimir Y. Ovchinnikov ◽  
Denis V. Antonets ◽  
Lyudmila F. Gulyaeva
Keyword(s):  
Transcriptional Activation ◽  
Binding Sites ◽  
In Silico ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Regulation Of Gene Expression ◽  
Experimental Studies ◽  
Transcriptional Level ◽  
Aryl Hydrocarbon ◽  
Exogenous Compounds

MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the post-transcriptional level. Many exogenous compounds or xenobiotics may affect microRNA expression. It is a well-established fact that xenobiotics with planar structure like TCDD, benzo(a)pyrene (BP) can bind aryl hydrocarbon receptor (AhR) followed by its nuclear translocation and transcriptional activation of target genes. Another chemically diverse group of xenobiotics including phenobarbital, DDT, can activate the nuclear receptor CAR and in some cases estrogen receptors ESR1 and ESR2. We hypothesized that such chemicals can affect miRNA expression through the activation of AHR, CAR, and ESRs. To prove this statement, we used in silico methods to find DRE, PBEM, ERE potential binding sites for these receptors, respectively. We have predicted AhR, CAR, and ESRs binding sites in 224 rat, 201 mouse, and 232 human promoters of miRNA-coding genes. In addition, we have identified a number of miRNAs with predicted AhR, CAR, and ESRs binding sites that are known as oncogenes and as tumor suppressors. Our results, obtained in silico, open a new strategy for ongoing experimental studies and will contribute to further investigation of epigenetic mechanisms of carcinogenesis.

scholarly journals The miRNA COMPLEXES AGAINST CORONAVIRUSES COVID-19, SARS-CoV, and MERS-CoV

2020 ◽  
Author(s):  
Anatoliy Ivashchenko ◽  
Aizhan Rakhmetullina ◽  
Aigul Akimniyazova ◽  
Dana Aisina ◽  
Anna Pyrkova
Keyword(s):  
Free Energy ◽  
Side Effects ◽  
Binding Sites ◽  
High Selectivity ◽  
High Concentration ◽  
Human Genes ◽  
Weak Binding ◽  
Simultaneous Inhibition

Abstract The possibility of using miRNA (mRNA-inhibiting RNA) to inhibit infections caused by the coronaviruses COVID-19, SARS-CoV, and MERS-CoV has been shown. Using bioinformatics approaches, completely complementary miRNA (cc-miRNA) complexes were predicted to be able to bind and inhibit the translation of coronavirus proteins and the replication of COVID-19, SARS-CoV, and MERS-CoV genomes. For complexes of seven cc-miRc for COVID-19, seven cc-miRs for SARS-CoV, and eight cc-miRm for MERS-CoV, the interactions with the RNA genomes (gRNAs) of the corresponding coronaviruses was evaluated. The free energy of the interactions of cc-miRNAs with binding sites was significantly higher than the free energy of the interactions with other regions in gRNA, which ensures high selectivity of the binding of cc-miRNAs. Weak binding of cc-miRNAs to the mRNAs of 17508 human genes was shown, which suggests the absence of side effects of the cc-miRNAs in humans. A feature of this method is the simultaneous inhibition of translation and replication by several cc-miRNAs binding from the 5' end to the 3' end of gRNA. The use of several cc-miRNAs to suppress infections allows each of them to be used at a lower concentration to avoid side effects when one cc-miRNA is introduced into humans at a high concentration.

scholarly journals Prediction of clusters of miRNA binding sites in mRNA candidate genes of breast cancer subtypes

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8049 ◽  
Author(s):  
Dana Aisina ◽  
Raigul Niyazova ◽  
Shara Atambayeva ◽  
Anatoliy Ivashchenko
Keyword(s):  
Breast Cancer ◽  
Candidate Genes ◽  
Binding Sites ◽  
Target Genes ◽  
Breast Cancer Subtype ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Nucleotide Binding Sites ◽  
Cancer Subtype ◽  
Gene Mrna

The development of breast cancer (BC) subtypes is controlled by distinct sets of candidate genes, and the expression of these genes is regulated by the binding of their mRNAs with miRNAs. Predicting miRNA associations and target genes is thus essential when studying breast cancer. The MirTarget program identifies the initiation of miRNA binding to mRNA, the localization of miRNA binding sites in mRNA regions, and the free energy from the binding of all miRNA nucleotides with mRNA. Candidate gene mRNAs have clusters (miRNA binding sites with overlapping nucleotide sequences). mRNAs of EPOR, MAZ and NISCH candidate genes of the HER2 subtype have clusters, and there are four clusters in mRNAs of MAZ, BRCA2 and CDK6 genes. Candidate genes of the triple-negative subtype are targets for multiple miRNAs. There are 11 sites in CBL mRNA, five sites in MMP2 mRNA, and RAB5A mRNA contains two clusters in each of the three sites. In SFN mRNA, there are two clusters in three sites, and one cluster in 21 sites. Candidate genes of luminal A and B subtypes are targets for miRNAs: there are 21 sites in FOXA1 mRNA and 15 sites in HMGA2 mRNA. There are clusters of five sites in mRNAs of ITGB1 and SOX4 genes. Clusters of eight sites and 10 sites are identified in mRNAs of SMAD3 and TGFB1 genes, respectively. Organizing miRNA binding sites into clusters reduces the proportion of nucleotide binding sites in mRNAs. This overlapping of miRNA binding sites creates a competition among miRNAs for a binding site. From 6,272 miRNAs studied, only 29 miRNAs from miRBase and 88 novel miRNAs had binding sites in clusters of target gene mRNA in breast cancer. We propose using associations of miRNAs and their target genes as markers in breast cancer subtype diagnosis.

scholarly journals Prediction of clusters of miRNA binding sites in mRNA candidate genes of breast cancer

2019 ◽  
Author(s):  
Dana Aisina ◽  
Raigul Niyazova ◽  
Shara Atambayeva ◽  
Anatoliy Ivashchenko
Keyword(s):  
Breast Cancer ◽  
Candidate Genes ◽  
Binding Sites ◽  
Target Genes ◽  
Untranslated Regions ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Nucleotide Binding Sites ◽  
Free Energy Of Binding ◽  
Triple Negative Subtype

Distinct sets of candidate genes control the development of breast cancer subtypes. The expression of many genes is regulated by the binding of their mRNAs with miRNAs. The prediction of miRNA associations and target genes is essential in studying of breast cancer. The MirTarget program defines the following features of binding miRNA to mRNA: the start of the initiation of miRNA binding to mRNA; the localization of miRNA binding sites in 5'-untranslated regions (5'UTR), coding domain sequences (CDS) and 3'-untranslated regions (3'UTR); the free energy of binding of all miRNA nucleotides with mRNA; the schemes of interactions of all miRNAs nucleotides with mRNAs. The mRNAs of many genes have clusters (miRNA binding sites with overlapping nucleotide sequences) located in 5'UTR, CDS, or 3'UTR. There are clusters in 5'UTR of mRNA EPOR, MAZ and NISCH candidate genes of HER2 subtype. There are four clusters in CDS of mRNA MAZ gene, and in 3'UTR of mRNA BRCA2 and CDK6 genes. Candidate genes of triple-negative subtype are targets for multiple miRNAs. In 5'UTR of mRNA СBL gene, there are 11 sites; the mRNA for MMP2 gene contains five sites; the mRNA of RAB5A gene contains two clusters each of three sites. In 3'UTR of mRNA SFN gene, there are two clusters, each of three sites, and one cluster of 21 sites. Candidate genes of luminal A and B subtypes are targets for miRNAs: there are 21 sites in 5'UTR of mRNA FOXA1 gene and mRNA HMGA2 gene contains 15 sites. There are clusters of five sites in CDS of mRNA ITGB1 gene and five sites in 3'UTR of mRNA SOX4 genes. Clusters of eight sites and ten sites are identified in 3'UTR of mRNA SMAD3 and TGFB1 genes, respectively. The organization of miRNA binding sites into clusters reduces the proportion of nucleotide binding sites in 5'UTR, CDS and 3'UTRs. This overlapping of miRNA binding sites creates a competition among miRNAs for the binding site. From 6,272 studied miRNAs only 29 miRNAs from miRBase and 88 novel miRNAs have binding sites in clusters of mRNA target genes of breast cancer.

scholarly journals The miRNA COMPLEXES AGAINST CORONAVIRUSES SARS-CoV-2, SARS-CoV, and MERS-CoV

2020 ◽  
Author(s):  
Aizhan Rakhmetullina ◽  
Anatoliy Ivashchenko ◽  
Aigul Akimniyazova ◽  
Dana Aisina ◽  
Anna Pyrkova
Keyword(s):  
Free Energy ◽  
Side Effects ◽  
Binding Sites ◽  
Untranslated Region ◽  
Messenger Rnas ◽  
High Concentration ◽  
Human Genes ◽  
Weak Binding ◽  
Simultaneous Inhibition ◽  
Interaction Free Energy

Abstract Background: In the past twenty years humankind has effected from infections caused by SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome) and SARS-CoV-2 coronaviruses, which have caused significant harm to human health and resulted in high mortality. The possibility of using miRNA (mRNA-inhibiting RNA) to inhibit infections caused by the coronaviruses SARS-CoV-2, SARS-CoV, and MERS-CoV has been shown. Methods: The MirTarget program determines the following characteristics of interaction between miRNAs and messenger RNAs (mRNAs): the start of the miRNA binding site on the mRNA; the locations of the miRNA binding sites in the 3'-untranslated region (3'UTR), 5'-untranslated region (5'UTR), or coding sequence (CDS); the interaction free energy (∆G, kJ/mole); and nucleotide interaction schemes between miRNAs and mRNAs.Results: Using bioinformatics approaches, completely complementary miRNA (cc-miRNA) complexes were predicted to be able to bind and inhibit the translation of coronavirus proteins and the replication of SARS-CoV-2, SARS-CoV, and MERS-CoV genomes. For complexes of seven completely complementary miRNA of SARS-CoV-2 (cc-miRc), seven completely complementary miRNA of SARS-CoV (cc-miRs), and eight completely complementary miRNA of MERS-CoV (cc-miRm), the interactions with the RNA genomes (gRNAs) of the corresponding coronaviruses was evaluated. The free energy of the interactions of cc-miRNAs with binding sites was significantly higher than the free energy of the interactions with other regions in gRNA, which ensures high selectivity of the binding of cc-miRNAs. Weak binding of cc-miRNAs to the mRNAs of 17508 human genes was shown, which suggests the absence of side effects of the cc-miRNAs in humans. A feature of this method is the simultaneous inhibition of translation and replication by several cc-miRNAs binding from the 5' end to the 3' end of gRNA. Conclusion: The use of several cc-miRNAs to suppress infections allows each of them to be used at a lower concentration to avoid side effects when one cc-miRNA is introduced into humans at a high concentration.

scholarly journals FEATURES OF miRNA ASSOCIATIONS WITH mRNA OF MYOCARDIAL INFARCTION CANDIDATE GENES

REPORTS ◽  
2021 ◽  
Vol 2 (336) ◽  
pp. 46-53
Author(s):  
D. D. Mukushkina ◽  
A. T. Ivashchenko ◽  
S. Labeit
Keyword(s):  
Myocardial Infarction ◽  
Candidate Genes ◽  
Genetic Markers ◽  
Binding Sites ◽  
Target Genes ◽  
Thrombus Formation ◽  
Actual Problem ◽  
Inflammatory Reactions ◽  
Common Causes ◽  
Energy Of Interaction

Cardiovascular diseases, in particular myocardial infarction, are one of the most common causes of death in the world. To date, the risk assessment strategy infarction and post-infarction complications represent a significant problem sensitivity and predictive value of modern methods and markers, so the identification of new genetic markers is an actual problem. In this research, functionally significant candidate genes were studied, which are involved in the processes associated with the pathogenesis of myocardial infarction, in lipid metabolism, thrombus formation, endothelial dysfunction, and inflammatory reactions. However, in addition to genes, it has been determined that miRNA is also involved in the development of myocardial infarction by regulating the expression of target genes. This paper presents characteristics of miRNA interactions with mRNAs of candidate myocardial infarction genes. We have identified 34, 51 and 36 target genes that have miRNA binding sites in the 5'UTR, CDS, and 3'UTR regions, respectively. Based on the criteria chosen in our study, candidate genes were identified that have a free energy of interaction with miRNA equal to -120 kJ/mole and higher in the following associations: in 5’UTR - ID02142.3p-miR and ALDH2; ID00909.3p-miR and ALOX5; ID00216.3p-miR and CD40; ID01272.3p-miR and DDAH2; ID01774.5p-miR and IL6R; miR-6752-5p and KLF4; ID03332.3p-miR and LAMA3; ID02363.5p-miR and NOS3; ID02800.3p-miR and OPA1; ID01310.3p-miR and PDE4D; ID03397.3p-miR and PTGS2; ID01098.3p-miR and SERPINE1; ID01018.3p-miR and SGPP1; ID02430.3p-miR and SHH; ID01652.3p-miR and THBS1; ID01770.3p-miR and ZNF202; in CDS - ID00457.3p-miR and APOA1; ID00425.5p-miR and BTN2A1; ID01632.5p- miR and CCL5; ID02899.3p-miR and CDKN2B; miR-6894-5p and CYP1A2; ID01806.3p-miR and IL6R; ID01403.5p-miR and PLAUR; ID02950.3p-miR and SEMA3F; ID03332.3p-miR and SGPP1; ID02062.3p-miR and SIRT6; ID02050.3p-miR and TNF; ID01804.3p-miR and XBP1; ID00182.5p-miR and ZNF202; in 3’UTR - ID01293.5p-miR and SMTN; ID01882.5p-miR and TNNI3. The identified associations can be used as genetic markers in the diagnosis of myocardial infarction.

scholarly journals CHARACTERISTICS OF miRNA INTERACTION WITH mRNA OF ISCHEMIC HEART DISEASE CANDIDATE GENES

REPORTS ◽  
2021 ◽  
Vol 335 (1) ◽  
pp. 74-82
Author(s):  
D.D. Mukushkina ◽  
S. Labeit ◽  
A.T. Ivashchenko
Keyword(s):  
Free Energy ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Candidate Genes ◽  
Target Genes ◽  
Molecular Genetic ◽  
Ischemic Heart ◽  
Development Processes ◽  
Energy Of Interaction ◽  
And Oxidative Stress

Ischemic heart disease (IHD) is the most serious cardiovascular disease and one of the leading causes of death worldwide. An important role in the pathophysiology of IHD play such processes as the processes of inflammation and immune response, metabolism of homocysteine and folate, development processes of endothelial dysfunction and oxidative stress and homeostasis system. Accordingly, the identified genes that are directly involved in these processes. In addition, miRNA (mRNA-inhibiting RNA) may affect the expression of these candidate genes. Using bioinformatics methods, the most efficient associations of miRNA and target genes were established. This research presents the characteristics of miRNA interactions with mRNA of candidate IHD genes. Candidate genes were identified that had a free energy of interaction with miRNA equal to -120 kJ / mole and higher in the following interactions: in 5’UTR - ALDH2 and ID02142.3p-miR; CELSR2 and ID00457.3p-miR; DDAH2 and ID01272.3p-miR; DNMT1 and ID02052.5p-miR; DOCK7 and ID00061.3p-miR; EGFR and ID02457.3p-miR; FOLH1 and ID01428.3p-miR; IL6R and miR-6089; NOS3 and ID02363.5p-miR; NPC1 and ID00551.3p-miR; PPP1R17 and ID01693.5p-miR; PRKCH and ID00520.5p-miR; SERPINE1 and ID01098.3p-miR; in CDS - ABCG8 and ID03064.3p-miR; ADORA2A and ID02697.3p-miR; APOA1 and ID00457.3p-miR; CDKN2B and ID02899.3p-miR; IL6R and ID01806.3p-miR; TIMP2 and ID00098.5p-miR; TNF and ID02050.3p-miR; TRIB1 and ID03208.5p-miR; VWF and ID01238.5p-miR. Associations were also revealed in the 3'UTR region with an interaction free energy of -115 kJ/mole and higher: AGTR2 and ID01213.5p-miR; APLNR and ID00616.5p-miR; CXCL12 and ID00483.3p-miR; FADS2 and miR-1224-3p; FCGR2A and miR-1273g-3p; GCKR and ID02928.3p-miR; IL6R and ID00913.5p-miR; KCNJ11 and ID03288.5p-miR; PPP1R3B and ID00913.5p-miR; TFPI and miR-1273g-3p; TIMP2 and ID01941.5p-miR. The results obtained could be used as molecular genetic markers of IHD for the diagnosis of this disease.

scholarly journals Prediction of clusters of miRNA binding sites in mRNA candidate genes of breast cancer

2019 ◽  
Author(s):  
Dana Aisina ◽  
Raigul Niyazova ◽  
Shara Atambayeva ◽  
Anatoliy Ivashchenko
Keyword(s):  
Breast Cancer ◽  
Candidate Genes ◽  
Binding Sites ◽  
Target Genes ◽  
Untranslated Regions ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Nucleotide Binding Sites ◽  
Free Energy Of Binding ◽  
Triple Negative Subtype

Distinct sets of candidate genes control the development of breast cancer subtypes. The expression of many genes is regulated by the binding of their mRNAs with miRNAs. The prediction of miRNA associations and target genes is essential in studying of breast cancer. The MirTarget program defines the following features of binding miRNA to mRNA: the start of the initiation of miRNA binding to mRNA; the localization of miRNA binding sites in 5'-untranslated regions (5'UTR), coding domain sequences (CDS) and 3'-untranslated regions (3'UTR); the free energy of binding of all miRNA nucleotides with mRNA; the schemes of interactions of all miRNAs nucleotides with mRNAs. The mRNAs of many genes have clusters (miRNA binding sites with overlapping nucleotide sequences) located in 5'UTR, CDS, or 3'UTR. There are clusters in 5'UTR of mRNA EPOR, MAZ and NISCH candidate genes of HER2 subtype. There are four clusters in CDS of mRNA MAZ gene, and in 3'UTR of mRNA BRCA2 and CDK6 genes. Candidate genes of triple-negative subtype are targets for multiple miRNAs. In 5'UTR of mRNA СBL gene, there are 11 sites; the mRNA for MMP2 gene contains five sites; the mRNA of RAB5A gene contains two clusters each of three sites. In 3'UTR of mRNA SFN gene, there are two clusters, each of three sites, and one cluster of 21 sites. Candidate genes of luminal A and B subtypes are targets for miRNAs: there are 21 sites in 5'UTR of mRNA FOXA1 gene and mRNA HMGA2 gene contains 15 sites. There are clusters of five sites in CDS of mRNA ITGB1 gene and five sites in 3'UTR of mRNA SOX4 genes. Clusters of eight sites and ten sites are identified in 3'UTR of mRNA SMAD3 and TGFB1 genes, respectively. The organization of miRNA binding sites into clusters reduces the proportion of nucleotide binding sites in 5'UTR, CDS and 3'UTRs. This overlapping of miRNA binding sites creates a competition among miRNAs for the binding site. From 6,272 studied miRNAs only 29 miRNAs from miRBase and 88 novel miRNAs have binding sites in clusters of mRNA target genes of breast cancer.

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