Micro-RNAs: viral genome and robustness of gene expression in the host

2009 ◽  
Vol 367 (1908) ◽  
pp. 4941-4965 ◽  
Author(s):  
Jacques Demongeot ◽  
Emmanuel Drouet ◽  
Adrien Elena ◽  
Andrès Moreira ◽  
Yassine Rechoum ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Viral Genome ◽  
Protein Translation ◽  
Feedback Loops ◽  
Micro Rna ◽  
Rna Transcription ◽  
Viral Genomes ◽  
Micro Rnas ◽  
Ubiquitous Proteins

For comparing RNA rings or hairpins with reference or random ring sequences, circular versions of distances and distributions like those of Hamming and Gumbel are needed. We define these circular versions and we apply these new tools to the comparison of RNA relics (such as micro-RNAs and tRNAs) with viral genomes that have coevolved with them. Then we show how robust are the regulation networks incorporating in their boundary micro-RNAs as sources or new feedback loops involving ubiquitous proteins like p53 (which is a micro-RNA transcription factor) or oligopeptides regulating protein translation. Eventually, we propose a new coevolution game between viral and host genomes.

Abstract WMP80: Micro RNA-Therapy in Murine Thromboembolic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Kumar Vaibhav ◽  
Shannon Williams ◽  
Sumbul Fatima ◽  
Babak Baban ◽  
Krishnan M Dhandapani ◽  
...  
Keyword(s):  
Target Genes ◽  
Infarct Volume ◽  
Protein Translation ◽  
Micro Rna ◽  
Thromboembolic Stroke ◽  
Gene Expressions ◽  
Mirna Array ◽  
Micro Rnas ◽  
Pai 1

Background: Micro RNAs (miRNAs) could target multiple mRNAs, repressing the protein translation. We report acute changes in humoral miRNAome in a murine thromboembolic stroke model (eMCAo), and demonstrate the benefits of miRNA therapy in improving cerebral blood flow (CBF). Methods: Non-biased micro RNA (miRNA) array and bioinformatics analysis was performed in plasma collected at 4h post-eMCAo from male mice (C57/B6, 16-weeks). Individual PCR for miRNAs was also performed in brain tissues at 24h post-eMCAo. Moreover, frozen human plasma samples collected at ~4.5h post-stroke were also used for miRNA analysis. Finally, the miRNA mimic that was predicted to target genes of our interest was also tested in vivo and in vitro . Results: Principal component analysis (PCA) of the miRNA-array showed ~68% variance in the humoral miRNAome 4h after eMCAo in mice, and a significant change in Stroke vs. Sham groups (Cut off value >2 fold; p<0.05). Of interest, the hairpin precursor of miR-449b was downregulated (~2.35 fold, p<0.05) at 4h post-eMCAo, while the mature miR-449b was also significantly reduced at 24h post-eMCAo. Mature miR-449b was significantly reduced in human stroke plasma, too. In human brain endothelial cells, miR-449b mimic downregulated gene expressions of both plasminogen activator inhibitor (PAI-1) and alpha 2- antiplasmin (α-AP) only in hypoxia but not during normoxia. Therefore, we finally tested the cholesterol-conjugated miR-449b mimic in the murine eMCAo model. Pre-treatment with miR-449b mimic (8 mg/kg bwt) increased the absolute CBF and reduced edema (as determined by MRI), and also improved the neurological outcomes and reduced % infarct volume (p<0.05). Results: The miR-449b mimic could be a possible therapy to suppress aberrant gene expressions of PAI-1 and α-AP, which will allow more spontaneous reperfusion and benefits from low dose tPA.

scholarly journals MicroRNAs: regulators of gene expression and cell differentiation

Blood ◽  
2006 ◽  
Vol 108 (12) ◽  
pp. 3646-3653 ◽  
Author(s):  
Ramesh A. Shivdasani
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
Protein Translation ◽  
Specific Aspect ◽  
Mirna Biogenesis ◽  
Mirna Regulation ◽  
Protein Coding ◽  
Rna Molecules ◽  
Protein Levels ◽  
Micro Rnas

AbstractThe existence and roles of a class of abundant regulatory RNA molecules have recently come into sharp focus. Micro-RNAs (miRNAs) are small (approximately 22 bases), non–protein-coding RNAs that recognize target sequences of imperfect complementarity in cognate mRNAs and either destabilize them or inhibit protein translation. Although mechanisms of miRNA biogenesis have been elucidated in some detail, there is limited appreciation of their biological functions. Reported examples typically focus on miRNA regulation of a single tissue-restricted transcript, often one encoding a transcription factor, that controls a specific aspect of development, cell differentiation, or physiology. However, computational algorithms predict up to hundreds of putative targets for individual miRNAs, single transcripts may be regulated by multiple miRNAs, and miRNAs may either eliminate target gene expression or serve to finetune transcript and protein levels. Theoretical considerations and early experimental results hence suggest diverse roles for miRNAs as a class. One appealing possibility, that miRNAs eliminate low-level expression of unwanted genes and hence refine unilineage gene expression, may be especially amenable to evaluation in models of hematopoiesis. This review summarizes current understanding of miRNA mechanisms, outlines some of the important outstanding questions, and describes studies that attempt to define miRNA functions in hematopoiesis.

scholarly journals Cerberus–Nodal–Lefty–Pitx signaling cascade controls left–right asymmetry in amphioxus

2017 ◽  
Vol 114 (14) ◽  
pp. 3684-3689 ◽  
Author(s):  
Guang Li ◽  
Xian Liu ◽  
Chaofan Xing ◽  
Huayang Zhang ◽  
Sebastian M. Shimeld ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Feedback Loops ◽  
Signaling Cascade ◽  
Nodal Signaling ◽  
Transcription Activator ◽  
Gene Expression Cassette ◽  
Left Right Asymmetry ◽  
The Right ◽  
Target Transcription Factor

Many bilaterally symmetrical animals develop genetically programmed left–right asymmetries. In vertebrates, this process is under the control of Nodal signaling, which is restricted to the left side by Nodal antagonists Cerberus and Lefty. Amphioxus, the earliest diverging chordate lineage, has profound left–right asymmetry as a larva. We show that Cerberus, Nodal, Lefty, and their target transcription factor Pitx are sequentially activated in amphioxus embryos. We then address their function by transcription activator-like effector nucleases (TALEN)-based knockout and heat-shock promoter (HSP)-driven overexpression. Knockout of Cerberus leads to ectopic right-sided expression of Nodal, Lefty, and Pitx, whereas overexpression of Cerberus represses their left-sided expression. Overexpression of Nodal in turn represses Cerberus and activates Lefty and Pitx ectopically on the right side. We also show Lefty represses Nodal, whereas Pitx activates Nodal. These data combine in a model in which Cerberus determines whether the left-sided gene expression cassette is activated or repressed. These regulatory steps are essential for normal left–right asymmetry to develop, as when they are disrupted embryos may instead form two phenotypic left sides or two phenotypic right sides. Our study shows the regulatory cassette controlling left–right asymmetry was in place in the ancestor of amphioxus and vertebrates. This includes the Nodal inhibitors Cerberus and Lefty, both of which operate in feedback loops with Nodal and combine to establish asymmetric Pitx expression. Cerberus and Lefty are missing from most invertebrate lineages, marking this mechanism as an innovation in the lineage leading to modern chordates.

scholarly journals Integrative p53, micro-RNA and Cathepsin Protease Co-Regulatory Expression Networks in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3454
Author(s):  
Surinder M. Soond ◽  
Maria V. Kozhevnikova ◽  
Paul A. Townsend ◽  
Andrey A. Zamyatnin
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Cancer Progression ◽  
Biological Effects ◽  
Micro Rna ◽  
Cathepsin Proteases ◽  
Micro Rnas ◽  
Significant Interest ◽  
Cathepsin Protease

As the direct regulatory role of p53 and some of its isoform proteins are becoming established in modulating gene expression in cancer research, another aspect of this mode of gene regulation that has captured significant interest over the years is the mechanistic interplay between p53 and micro-RNA transcriptional regulation. The input of this into modulating gene expression for some of the cathepsin family members has been viewed as carrying noticeable importance based on their biological effects during normal cellular homeostasis and cancer progression. While this area is still in its infancy in relation to general cathepsin gene regulation, we review the current p53-regulated micro-RNAs that are generating significant interest through their regulation of cathepsin proteases, thereby strengthening the link between activated p53 forms and cathepsin gene regulation. Additionally, we extend our understanding of this developing relationship to how such micro-RNAs are being utilized as diagnostic or prognostic tools and highlight their future uses in conjunction with cathepsin gene expression as potential biomarkers within a clinical setting.

Differential expression of micro-RNA in tumor and non-tumor tissues of patients with colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13516-e13516
Author(s):  
Inna A. Novikova ◽  
Natalya N. Timoshkina ◽  
Oleg Ivanovich Kit ◽  
Sergey I. Poluektov ◽  
Andrey V. Dashkov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Differential Expression ◽  
Tumor Markers ◽  
Target Genes ◽  
Tumor Tissue ◽  
Micro Rna ◽  
Differentially Expressed ◽  
Tumor Tissues ◽  
Micro Rnas

e13516 Background: The colorectal cancer (CRC) incidence is steadily increasing. Moreover, the problem of its early diagnosis remains unresolved due to the low specificity of known tumor markers, and the problem of creating new therapeutic approaches is due to the lack of a complete understanding of the mechanisms of regulation of gene expression in this oncopathology. The study of micro-RNAs (short non-coding RNAs that regulate gene expression) can be the solution to both problems. The aim of the study was to analyze micro-RNA differential expression in the tumor and non-tumor tissues of CRC patients. Methods: 5 patients with CRC (colon adenocarcinoma, G2) were selected for the multiple parallel micro-RNA sequencing. The mirVana miRNA Isolation Kit protocol was used to isolate small RNA fractions. The miRNA library was prepared using the TruSeq Small RNASample Preparation Kit. Sequencing of the nucleotide sequences of cDNA libraries was performed using a MiSeq (Illumina, USA). The copy numbers of micro-RNA were determined by comparing the nucleotide sequence of the sequenced molecules in each sample with the known nucleotide sequences of micro-RNA presented in the databases. When analyzing the differential expression of micro-RNA, the DESeq2 method implemented in R medium was used. Results: Six differentially expressed micro-RNAs were detected (p < 0.05): 2 that decrease expression (hsa-miR-143-3p,hsa-miR-26a-5p) and 4 increase expression in the tumor relative to non-tumor (hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-21-5p, hsa-let-7i-5p). The highest level of expression in both tumor and non-tumor tissue was observed for hsa-miR-143-3p, the lowest one for hsa-let-7i-5p. Moreover, the largest difference in micro-RNA expression in tumor tissue relative to non-tumor was shown for hsa-miR-92a-3p (4.5 times, p = 0.02), the smallest for hsa-miR-143-3p (2.4 times, p = 0.04). For miRNAs that differentially changed their expression, a search was made for target genes using the miRWalk 3.0 database. 14573 target genes were found, of which 3346 were for hypo-expressed micro-RNAs and 11228 for hyper-expressed micro-RNAs. Conclusions: Sequencing revealed 6 differentially expressed micro-RNAs (hsa-miR-143-3p, hsa-miR-26a-5p, hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-21-5p, hsa-let-7i-5p) in the tumor tissue is relatively non-tumor tissues of the colon. The data obtained expand the understanding of the mechanisms of gene regulation in the context of this oncopathology and may possibly become the basis for highly specific tumor markers panel.

scholarly journals Progress in micro RNA focused research in endocrinology

2016 ◽  
Vol 50 (2) ◽  
pp. 83-105 ◽  
Author(s):  
K. Voglova ◽  
J. Bezakova ◽  
Iveta Herichova
Keyword(s):  
Gene Expression ◽  
Physiological Role ◽  
Micro Rna ◽  
Mirna Biogenesis ◽  
Rna Molecules ◽  
Micro Rnas ◽  
Influence Gene Expression

AbstractMicro RNAs (miRNAs) are small regulatory molecules of increasing biologists’ interest. miRNAs, unlikely mRNA, do not encode proteins. It is a class of small double stranded RNA molecules that via their seed sequence interact with mRNA and inhibit its expression. It has been estimated that 30% of human gene expression is regulated by miRNAs. One miRNA usually targets several mRNAs and one mRNA can be regulated by several miRNAs. miRNA biogenesis is realized by key enzymes, Drosha and Dicer. miRNA/mRNA interaction depends on binding to RNA-induced silencing complex. Today, complete commercially available methodical proposals for miRNA investigation are available. There are techniques allowing the identification of new miRNAs and new miRNA targets, validation of predicted targets, measurement of miRNAs and their precursor levels, and validation of physiological role of miRNAs under in vitro and in vivo conditions. miRNAs have been shown to influence gene expression in several endocrine glands, including pancreas, ovary, testes, hypothalamus, and pituitary.

Sign in / Sign up

Export Citation Format

Share Document