scholarly journals CHARACTERISTICS OF miRNA INTERACTION WITH mRNA GENES OF T. AESTIVUM C2H2, ERF, GRAS TRANSCRIPTION FACTORS FAMILIES

2020 ◽  
Vol 2 (338) ◽  
pp. 5-11
Author(s):  
A. K. Rakhmetullina ◽  
S. K. Turasheva ◽  
A. A. Bolshoy ◽  
A. T. Ivashchenko
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Abiotic And Biotic Stresses ◽  
Biotic Stresses ◽  
Gras Family ◽  
Physiological Processes ◽  
Nucleotide Interactions

The molecular mechanisms for increasing plant productivity remain poorly understood. Genes of C2H2, GRAS, ERF transcription factors (TFs) families play a key role in the physiological processes of plants, including wheat. In recent years, the important role of miRNAs in the regulation of the expression of many genes involved in the formation of productivity has been established. Wheat miRNA (mRNA-inhibiting RNA) target genes are involved in the regulation of the development of flowers, seeds, root, shoots, and responses to abiotic and biotic stresses. The miRNAs binding sites in mRNAs of C2H2, ERF, GRAS TFs families were performed using the MirTarget program, which calculates the free energy of miRNA binding with mRNA, the schemes and positions of nucleotide interactions with binding sites. Wheat genes were used as the object of the study, since wheat is one of the main grain crops in Kazakhstan and in many other countries. The presence of miRNA binding sites with high nucleotide complementarity in mRNA of C2H2, ERF, GRAS TF genes of wheat was shown. All binding sites of these miRNAs were located in the CDS of mRNA target genes. Of the 125 miRNAs of T. aestivum, miR319-3p efficiently bound with mRNA of C2H2 family genes with the value of ΔG/ΔGm equal 91 %. miR7757-5p interacted with mRNA of ERF and GRAS family genes with the value of ΔG/ΔGm equal to 92 % and 90 % respectively. miR9778-5p bound with mRNA of C2H2, ERF, GRAS family genes to varying degrees. Each of the miR408-3p, miR9780-3p, and miR9778-5p had four target genes with the value of ΔG/ΔGm equal to 87 % and 89 %. These data indicate the dependency of C2H2, GRAS, ERF TFs families expression on miRNA. The obtained results expand the fundamental ideas about the regulatory mechanisms of miRNA in the process of plant growth and development.

scholarly journals tRFtarget: a database for transfer RNA-derived fragment targets

2020 ◽  
Vol 49 (D1) ◽  
pp. D254-D260 ◽  
Author(s):  
Ningshan Li ◽  
Nayang Shan ◽  
Lingeng Lu ◽  
Zuoheng Wang
Keyword(s):  
Binding Sites ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Target Prediction ◽  
Transfer Rna ◽  
Web Based ◽  
New Class ◽  
Physiological Processes ◽  
Graphic Illustration ◽  
Functional Pathway

Abstract Transfer RNA-derived fragments (tRFs) are a new class of small non-coding RNAs and play important roles in biological and physiological processes. Prediction of tRF target genes and binding sites is crucial in understanding the biological functions of tRFs in the molecular mechanisms of human diseases. We developed a publicly accessible web-based database, tRFtarget (http://trftarget.net), for tRF target prediction. It contains the computationally predicted interactions between tRFs and mRNA transcripts using the two state-of-the-art prediction tools RNAhybrid and IntaRNA, including location of the binding sites on the target, the binding region, and free energy of the binding stability with graphic illustration. tRFtarget covers 936 tRFs and 135 thousand predicted targets in eight species. It allows researchers to search either target genes by tRF IDs or tRFs by gene symbols/transcript names. We also integrated the manually curated experimental evidence of the predicted interactions into the database. Furthermore, we provided a convenient link to the DAVID® web server to perform downstream functional pathway analysis and gene ontology annotation on the predicted target genes. This database provides useful information for the scientific community to experimentally validate tRF target genes and facilitate the investigation of the molecular functions and mechanisms of tRFs.

Mechanisms of Transcriptional Regulation and Transformation by HOXA9

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-30-SCI-30
Author(s):  
Jay L. Hess ◽  
Cailin Collins ◽  
Joel Bronstein ◽  
Yuqing Sun ◽  
Surya Nagaraja
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Target Genes ◽  
Conflicts Of Interest ◽  
Hematopoietic Stem ◽  
A Genome ◽  
The Impact

Abstract Abstract SCI-30 HOXA9 plays important roles in both development and hematopoiesis and is overexpressed in more than 50 percent of acute myeloid leukemias (AML). Nearly all cases of AML with mixed lineage leukemia (MLL) translocations show increased HOXA9 expression, as well as cases with mutation of the nucleophosmin gene NPM1, overexpression of CDX2, and fusions of NUP98. In most cases, upregulation of HOXA9 is accompanied by upregulation of its homeodomain-containing cofactor MEIS1, which directly interacts with HOXA9. While HOXA9 alone is sufficient for transformation of hematopoietic stem cells in culture, the addition of MEIS1 increases the transformation efficiency and results in rapidly fatal leukemias in transplanted animals. Despite the crucial role that HOXA9 plays in development, hematopoiesis, and leukemia, its transcriptional targets and mechanisms of action are poorly understood. We have used ChIP-seq to identify Hoxa9 and Meis1 binding sites on a genome-wide level in myeloblastic cells, profiled their associated epigenetic modifications, identified the target genes regulated by HOXA9 and identified HOXA9 interacting proteins. HOXA9 and MEIS1 cobind at hundreds of promoter distal, highly evolutionarily conserved sites showing high levels of histone H3K4 monomethylation and CBP/P300 binding. These include many proleukemogenic gene loci, such as Erg, Flt3, Myb, Lmo2, and Sox4. In addition, HOXA9 binding sites overlap a subset of enhancers previously implicated in myeloid differentiation and inflammation. HOXA9 binding at enhancers stabilizes association of MEIS1 and lineage-restricted transcription factors, including C/EBPα, PU.1, and STAT5A/B thereby promoting CBP/p300 recruitment, histone acetylation, and transcriptional activation. Current efforts are focused on using both biochemical and genetic approaches to assess the role of HOXA9 “enhanceosome” components C/EBPα, PU.1, and STAT5A/B in transcriptional regulation and leukemogenesis. Studies to date suggest that C/EBPα and PU.1 binding can occur in the absence of HOXA9/MEIS1, supporting a model in which these proteins act as pioneer transcription factors for establishment of poised, but not activated, HOXA9-regulated enhancers. Work is under way to assess the impact of high-level HOXA9 and MEIS1 on enhanceosome assembly and the role of recruitment of transcriptional coactivators involved in target gene up- or downregulation, including histone acetyltransferases and chromatin remodeling complexes. Collectively, our findings suggest that HOXA9-regulated enhancers are a fundamental mechanism of HOX-mediated transcription in normal development that is deregulated in leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Transcription Factors in Plant Stress Responses: Challenges and Potential for Sugarcane Improvement

Plants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 491 ◽  
Author(s):  
Talha Javed ◽  
Rubab Shabbir ◽  
Ahmad Ali ◽  
Irfan Afzal ◽  
Uroosa Zaheer ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Stress Responses ◽  
Target Genes ◽  
Plant Stress ◽  
Growth And Yield ◽  
Abiotic And Biotic Stresses ◽  
Cis Acting ◽  
Biotic Stresses ◽  
Signal Perception ◽  
Wide Range

Increasing vulnerability of crops to a wide range of abiotic and biotic stresses can have a marked influence on the growth and yield of major crops, especially sugarcane (Saccharum spp.). In response to various stresses, plants have evolved a variety of complex defense systems of signal perception and transduction networks. Transcription factors (TFs) that are activated by different pathways of signal transduction and can directly or indirectly combine with cis-acting elements to modulate the transcription efficiency of target genes, which play key regulators for crop genetic improvement. Over the past decade, significant progresses have been made in deciphering the role of plant TFs as key regulators of environmental responses in particular important cereal crops; however, a limited amount of studies have focused on sugarcane. This review summarizes the potential functions of major TF families, such as WRKY, NAC, MYB and AP2/ERF, in regulating gene expression in the response of plants to abiotic and biotic stresses, which provides important clues for the engineering of stress-tolerant cultivars in sugarcane.

scholarly journals The role of m6A modification in the biological functions and diseases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiulin Jiang ◽  
Baiyang Liu ◽  
Zhi Nie ◽  
Lincan Duan ◽  
Qiuxia Xiong ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Rna Modification ◽  
Biological Functions ◽  
Rna Methylation ◽  
Downstream Target ◽  
Different Types ◽  
M6a Rna Methylation

AbstractN6-methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher eukaryotic cells. m6A modification is modified by the m6A methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and, removed by the demethylases, or erasers, including FTO and ALKBH5. It is recognized by m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1, also known as “readers”. Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions, especially in the initiation and progression of different types of human cancers. In this review, we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic, central nervous and reproductive systems. We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation, its regulators and downstream target genes, during cancer progression in above systems. We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.

scholarly journals High Energy Intake Induced Overexpression of Transcription Factors and Its Regulatory Genes Involved in Acceleration of Hepatic Lipogenesis: A Rat Model for Type 2 Diabetes

Biomedicines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 76 ◽  
Author(s):  
Suresh P. Khadke ◽  
Aniket A. Kuvalekar ◽  
Abhay M. Harsulkar ◽  
Nitin Mantri
Keyword(s):  
Type 2 Diabetes ◽  
Transcription Factors ◽  
Glucose Tolerance ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
High Energy ◽  
Tolerance Test ◽  
Diabetic Control ◽  
Ppar Γ

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by impaired insulin action and its secretion. The objectives of the present study were to establish an economical and efficient animal model, mimicking pathophysiology of human T2DM to understand probable molecular mechanisms in context with lipid metabolism. In the present study, male Wistar rats were randomly divided into three groups. Animals were fed with high fat diet (HFD) except healthy control (HC) for 12 weeks. After eight weeks, intra peritoneal glucose tolerance test was performed. After confirmation of glucose intolerance, diabetic control (DC) group was injected with streptozotocin (STZ) (35 mg/kg b.w., i.p.). HFD fed rats showed increase (p ≤ 0.001) in glucose tolerance and HOMA-IR as compared to HC. Diabetes rats showed abnormal (p ≤ 0.001) lipid profile as compared to HC. The hepatocyte expression of transcription factors SREBP-1c and NFκβ, and their target genes were found to be upregulated, while PPAR-γ, CPT1A and FABP expressions were downregulated as compared to the HC. A number of animal models have been raised for studying T2DM, but the study has been restricted to only the biochemical level. The model is validated at biochemical, molecular and histopathological levels, which can be used for screening new therapeutics for the effective management of T2DM.

scholarly journals Discovery of MicroRNAs and Their Target Genes Related to Drought in Paulownia “Yuza 1” by High-Throughput Sequencing

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Minjie Deng ◽  
Yabing Cao ◽  
Zhenli Zhao ◽  
Lu Yang ◽  
Yanfang Zhang ◽  
...  
Keyword(s):  
Drought Stress ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Plant Hormone ◽  
Target Genes ◽  
Reference Data ◽  
Relevant Information ◽  
Putative Target

Understanding the role of miRNAs in regulating the molecular mechanisms responsive to drought stress was studied in Paulownia “yuza 1.” Two small RNA libraries and two degradome libraries were, respectively, constructed and sequenced in order to detect miRNAs and their target genes associated with drought stress. A total of 107 miRNAs and 42 putative target genes were identified in this study. Among them, 77 miRNAs were differentially expressed between drought-treated Paulownia “yuza 1” and the control (60 downregulated and 17 upregulated). The predicted target genes were annotated using the GO, KEGG, and Nr databases. According to the functional classification of the target genes, Paulownia “yuza 1” may respond to drought stress via plant hormone signal transduction, photosynthesis, and osmotic adjustment. Furthermore, the expression levels of seven miRNAs (ptf-miR157b, ptf-miR159b, ptf-miR398a, ptf-miR9726a, ptf-M2153, ptf-M2218, and ptf-M24a) and their corresponding target genes were validated by quantitative real-time PCR. The results provide relevant information for understanding the molecular mechanism of Paulownia resistance to drought and reference data for researching drought resistance of other trees.

scholarly journals Low-affinity transcription factor binding sites shape morphogen responses and enhancer evolution

2013 ◽  
Vol 368 (1632) ◽  
pp. 20130018 ◽  
Author(s):  
Andrea I. Ramos ◽  
Scott Barolo
Keyword(s):  
Transcription Factor ◽  
Binding Affinity ◽  
Binding Sites ◽  
Target Genes ◽  
Gene Activation ◽  
Transcriptional Response ◽  
Morphogen Gradients ◽  
Weak Binding ◽  
Initial Hypothesis

In the era of functional genomics, the role of transcription factor (TF)–DNA binding affinity is of increasing interest: for example, it has recently been proposed that low-affinity genomic binding events, though frequent, are functionally irrelevant. Here, we investigate the role of binding site affinity in the transcriptional interpretation of Hedgehog (Hh) morphogen gradients . We noted that enhancers of several Hh-responsive Drosophila genes have low predicted affinity for Ci, the Gli family TF that transduces Hh signalling in the fly. Contrary to our initial hypothesis, improving the affinity of Ci/Gli sites in enhancers of dpp , wingless and stripe , by transplanting optimal sites from the patched gene, did not result in ectopic responses to Hh signalling. Instead, we found that these enhancers require low-affinity binding sites for normal activation in regions of relatively low signalling. When Ci/Gli sites in these enhancers were altered to improve their binding affinity, we observed patterning defects in the transcriptional response that are consistent with a switch from Ci-mediated activation to Ci-mediated repression. Synthetic transgenic reporters containing isolated Ci/Gli sites confirmed this finding in imaginal discs. We propose that the requirement for gene activation by Ci in the regions of low-to-moderate Hh signalling results in evolutionary pressure favouring weak binding sites in enhancers of certain Hh target genes.

scholarly journals Role of Cytokines and Transcription Factors in Periodontitis: A Review of Cellular and Molecular Mechanisms

2015 ◽  
Vol 11 (4) ◽  
pp. 125-138
Author(s):  
Anne Carolina Eleutério Leite ◽  
Valéria Martins de Araújo Carneiro ◽  
Júlia Faria Nunes ◽  
André Cruz de Sousa ◽  
Maria Imaculada Muniz-Junqueira ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms

Abstract W MP86: Microrna-146a Modulates Neurogenesis And Oligodendrogenesis After Stroke

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Xianshuang Liu ◽  
Chopp Michael ◽  
Xinli Wang ◽  
Li Zhang ◽  
Yisheng Cui ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Target Genes ◽  
Artery Occlusion ◽  
Locked Nucleic Acid ◽  
Myelin Proteins ◽  
Oligodendrocyte Progenitor Cells ◽  
Marker Proteins

Background: Neurogenesis and oligodendrogenesis are associated with functional recovery after stroke. However, the molecules that regulate the generation of new neurons and oligodendrocytes have not been fully investigated. MicroRNAs (miRNAs) post-transcriptionally regulate gene expression. MiR-146a has been reported to regulate the immune response in cells, but the role of miR-146a in neural (NPCs) and oligodendrocyte progenitor cells (OPCs) remains unexplored. Methods and Results: Adult Wistar rats were subjected to right middle cerebral artery occlusion (MCAo). In situ hybridization using locked nucleic acid (LNA)probes against miR-146a showed that stroke considerably increased miR-146a density in the subventricular zone (SVZ, 19 ± 1 vs 6 ± 0.1 area/mm2 in non-MCAo group, p<0.05, n=4/group) and corpus callosum (24 ± 3 vs 8±1 area/mm2 in non-MCAo group) of the ischemic hemisphere. Quantitative RT-PCR also demonstrated a marked upregulation of miR-146a transcript in ischemic NPCs (8.5 fold), suggesting an important role in stroke-induced neurogenesis and oligodendrogenesis. To test its biological function, we over-expressed miR-146a in neural progenitor cells by transfection of miR-146a mimics using nucleofector and found that elevation of miR-146a significantly increased the percentage of Tuj1+ neuroblasts (5 ± 0.3 vs 1 ± 0.2%, p<0.05, n=6/group) and O4+ OPCs (10 ± 1 vs 4 ± 0.4%, p<0.05). Moreover, over-expression of miR-146a in primary cultured OPCs significantly increased several myelin proteins including MBP and PLP, and decreased levels of OPC marker proteins including PDGFRα and NG2, whereas attenuation of miR-146a by siRNA against miR-146a suppressed myelin proteins and augmented OPC marker proteins. Furthermore, miR-146a levels in the OPCs were inversely related to IRAK1 proteins, one of miR-146a target genes. Attenuation of IRAK1 in OPCs substantially increased myelin proteins, indicating that miR-146a mediates oligodendrocyte maturation via targeting IRAK1. Conclusion: Our data provide new insight into molecular mechanisms underlying stroke-induced neurogenesis and oligodendrogenesis by revealing a novel role of miR-146a in NPCs and OPCs, which has potential to be used as a new therapy for neurorecovery after stroke.

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