MicroRNAs in Development and Disease

2011 ◽  
Vol 91 (3) ◽  
pp. 827-887 ◽  
Author(s):  
Danish Sayed ◽  
Maha Abdellatif
Keyword(s):  
Gene Regulation ◽  
Mammalian Cells ◽  
Untranslated Region ◽  
Mirna Target ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Target Sites ◽  
Health And Disease ◽  
Additional Level ◽  
Made In

MicroRNAs (miRNAs) are a class of posttranscriptional regulators that have recently introduced an additional level of intricacy to our understanding of gene regulation. There are currently over 10,000 miRNAs that have been identified in a range of species including metazoa, mycetozoa, viridiplantae, and viruses, of which 940, to date, are found in humans. It is estimated that more than 60% of human protein-coding genes harbor miRNA target sites in their 3′ untranslated region and, thus, are potentially regulated by these molecules in health and disease. This review will first briefly describe the discovery, structure, and mode of function of miRNAs in mammalian cells, before elaborating on their roles and significance during development and pathogenesis in the various mammalian organs, while attempting to reconcile their functions with our existing knowledge of their targets. Finally, we will summarize some of the advances made in utilizing miRNAs in therapeutics.

Bioinformatics Methods for Studying MicroRNA and ARE-Mediated Regulation of Post-Transcriptional Gene Expression

2010 ◽  
Vol 1 (3) ◽  
pp. 97-112 ◽  
Author(s):  
Richipal Singh Bindra ◽  
Jason T. L. Wang ◽  
Paramjeet Singh Bagga
Keyword(s):  
Mirna Target ◽  
Target Prediction ◽  
Untranslated Regions ◽  
Regulatory Rna ◽  
Rna Motifs ◽  
Protein Coding ◽  
Rna Molecules ◽  
Cellular Processes ◽  
Target Sites ◽  
Transcriptional Gene Regulation

MicroRNAs (miRNAs) are short single-stranded RNA molecules with 21-22 nucleotides known to regulate post-transcriptional expression of protein-coding genes involved in most of the cellular processes. Prediction of miRNA targets is a challenging bioinformatics problem. AU-rich elements (AREs) are regulatory RNA motifs found in the 3’ untranslated regions (UTRs) of mRNAs, and they play dominant roles in the regulated decay of short-lived human mRNAs via specific interactions with proteins. In this paper, the authors review several miRNA target prediction tools and data sources, as well as computational methods used for the prediction of AREs. The authors discuss the connection between miRNA and ARE-mediated post-transcriptional gene regulation. Finally, a data mining method for identifying the co-occurrences of miRNA target sites in ARE containing genes is presented.

Regulation of microRNA biogenesis and function

2012 ◽  
Vol 107 (04) ◽  
pp. 605-610 ◽  
Author(s):  
Thomas Treiber ◽  
Nora Treiber ◽  
Gunter Meister
Keyword(s):  
Mammalian Cells ◽  
Untranslated Region ◽  
Protein Complexes ◽  
Mature Mirnas ◽  
Review Article ◽  
Cellular Functions ◽  
Target Sites ◽  
Cellular Pathways ◽  
And Function ◽  
Site Binding

SummaryMicroRNAs (miRNAs) are considered as key regulators of literally all cellular pathways. Therefore, miRNA biosynthesis and their individual cellular functions must be tightly regulated as well. MiRNAs are transcribed as primary transcripts, which are processed to mature miRNAs in two consecutive maturation steps. Finally, the mature miRNA is incorporated into a miRNA-protein complex, where it directly interacts with a member of the Argonaute (Ago) protein family. The miRNA guides such protein complexes to partial complementary target sites, which are typically located in the 3’ untranslated region (UTR) of mRNAs leading to inhibition of gene expression. MiRNA activity and abundance is regulated on various levels ranging from transcription and processing to target site binding and miRNA stability. Recent advances in our understanding of how miRNA activity is regulated in mammalian cells are summarised and discussed in this review article.

Role of autophagy in cancer prevention, development and therapy

2013 ◽  
Vol 55 ◽  
pp. 133-151 ◽  
Author(s):  
G. Vignir Helgason ◽  
Tessa L. Holyoake ◽  
Kevin M. Ryan
Keyword(s):  
Quality Control ◽  
Clinical Trials ◽  
Cancer Prevention ◽  
Mammalian Cells ◽  
Physiological Role ◽  
Anticancer Therapy ◽  
Substantial Progress ◽  
Health And Disease ◽  
Made In

Autophagy is a process that takes place in all mammalian cells and ensures homoeostasis and quality control. The term autophagy [self (auto)-eating (phagy)] was first introduced in 1963 by Christian de Duve, who discovered the involvement of lysosomes in the autophagy process. Since then, substantial progress has been made in understanding the molecular mechanism and signalling regulation of autophagy and several reviews have been published that comprehensively summarize these findings. The role of autophagy in cancer has received a lot of attention in the last few years and autophagy modulators are now being tested in several clinical trials. In the present chapter we aim to give a brief overview of recent findings regarding the mechanism and key regulators of autophagy and discuss the important physiological role of mammalian autophagy in health and disease. Particular focus is given to the role of autophagy in cancer prevention, development and in response to anticancer therapy. In this regard, we also give an updated list and discuss current clinical trials that aim to modulate autophagy, alone or in combination with radio-, chemo- or targeted therapy, for enhanced anticancer intervention.

Bioinformatics Methods for Studying MicroRNA and ARE-Mediated Regulation of Post-Transcriptional Gene Expression

2013 ◽  
pp. 156-173
Author(s):  
Richipal Singh Bindra ◽  
Jason T. L. Wang ◽  
Paramjeet Singh Bagga
Keyword(s):  
Mirna Target ◽  
Target Prediction ◽  
Specific Interactions ◽  
Rna Motifs ◽  
Protein Coding ◽  
Rna Molecules ◽  
Cellular Processes ◽  
Protein Coding Genes ◽  
Prediction Tools ◽  
Transcriptional Gene Regulation

MicroRNAs (miRNAs) are short single-stranded RNA molecules with 21-22 nucleotides known to regulate post-transcriptional expression of protein-coding genes involved in most of the cellular processes. Prediction of miRNA targets is a challenging bioinformatics problem. AU-rich elements (AREs) are regulatory RNA motifs found in the 3’ untranslated regions (UTRs) of mRNAs, and they play dominant roles in the regulated decay of short-lived human mRNAs via specific interactions with proteins. In this paper, the authors review several miRNA target prediction tools and data sources, as well as computational methods used for the prediction of AREs. The authors discuss the connection between miRNA and ARE-mediated post-transcriptional gene regulation. Finally, a data mining method for identifying the co-occurrences of miRNA target sites in ARE containing genes is presented.

Combinatorial effects of microRNAs to suppress the Myc oncogenic pathway

Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6255-6266 ◽  
Author(s):  
María J. Bueno ◽  
Marta Gómez de Cedrón ◽  
Gonzalo Gómez-López ◽  
Ignacio Pérez de Castro ◽  
Lorena Di Lisio ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Genetic Interactions ◽  
Target Protein ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Oncogenic Pathway ◽  
Target Sites ◽  
Reporter Assays

Abstract Many mammalian transcripts contain target sites for multiple miRNAs, although it is not clear to what extent miRNAs may coordinately regulate single genes. We have mapped the interactions between down-regulated miRNAs and overexpressed target protein-coding genes in murine and human lymphomas. Myc, one of the hallmark oncogenes in these lymphomas, stands out as the up-regulated gene with the highest number of genetic interactions with down-regulated miRNAs in mouse lymphomas. The regulation of Myc by several of these miRNAs is confirmed by cellular and reporter assays. The same approach identifies MYC and multiple Myc targets as a preferential target of down-regulated miRNAs in human Burkitt lymphoma, a pathology characterized by translocated MYC oncogenes. These results indicate that several miRNAs must be coordinately down-regulated to enhance critical oncogenes, such as Myc. Some of these Myc-targeting miRNAs are repressed by Myc, suggesting that these tumors are a consequence of the unbalanced activity of Myc versus miRNAs.

scholarly journals The distributions of protein coding genes within chromatin domains in relation to human disease

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Enrique M. Muro ◽  
Jonas Ibn-Salem ◽  
Miguel A. Andrade-Navarro
Keyword(s):  
Gene Regulation ◽  
Human Disease ◽  
Housekeeping Genes ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Genome Wide ◽  
General Rules ◽  
Functional Consequences ◽  
Disease Associated Genes

Abstract Background Our understanding of the nuclear chromatin structure has increased hugely during the last years mainly as a consequence of the advances in chromatin conformation capture methods like Hi-C. The unprecedented resolution of genome-wide interaction maps shows functional consequences that extend the initial thought of an efficient DNA packaging mechanism: gene regulation, DNA repair, chromosomal translocations and evolutionary rearrangements seem to be only the peak of the iceberg. One key concept emerging from this research is the topologically associating domains (TADs) whose functional role in gene regulation and their association with disease is not fully untangled. Results We report that the lower the number of protein coding genes inside TADs, the higher the tendency of those genes to be associated with disease (p-value = 4 × $$10^{-54}$$10-54). Moreover, housekeeping genes are less associated with disease than other genes. Accordingly, they are depleted in TADs containing less than three protein coding genes (p-value = 3.9 × $$10^{-34}$$10-34). We observed that TADs with higher ratios of enhancers versus genes contained higher numbers of disease-associated genes. We interpret these results as an indication that sharing enhancers among genes reduces their involvement in disease. Larger TADs would have more chances to accommodate many genes and select for enhancer sharing along evolution. Conclusions Genes associated with human disease do not distribute randomly over the TADs. Our observations suggest general rules that confer functional stability to TADs, adding more evidence to the role of TADs as regulatory units.

scholarly journals Long non-coding RNA gene regulation and trait associations across human tissues

2019 ◽  
Author(s):  
O. M. de Goede ◽  
N. M. Ferraro ◽  
D. C. Nachun ◽  
A. S. Rao ◽  
F. Aguet ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Transcriptional Activity ◽  
Biological Function ◽  
Cell Type ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Non Coding Rna ◽  
Regulation Network ◽  
Long Non Coding Rna ◽  
Trait Associations

AbstractLong non-coding RNA (lncRNA) genes are known to have diverse impacts on gene regulation. However, it is still a major challenge to distinguish functional lncRNAs from those that are byproducts of surrounding transcriptional activity. To systematically identify hallmarks of biological function, we used the GTEx v8 data to profile the expression, regulation, network relationships and trait associations of lncRNA genes across 49 tissues encompassing 87 distinct traits. In addition to revealing widespread differences in regulatory patterns between lncRNA and protein-coding genes, we identified novel disease-associated lncRNAs, such as C6orf3 for psoriasis and LINC01475/RP11-129J12.1 for ulcerative colitis. This work provides a comprehensive resource to interrogate lncRNA genes of interest and annotate cell type and human trait relevance.One Sentence SummarylncRNA genes have distinctive regulatory patterns and unique trait associations compared to protein-coding genes.

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