microRNA  (miRNA) reviews  (6)
microRNA  (miRNA)   &   quantitative real-time RT-PCR (1)
microRNA  (miRNA)   &   quantitative real-time RT-PCR (2)
microRNA  (miRNA)   &   quantitative real-time RT-PCR (3)
microRNA  (miRNA)   &   quantitative real-time RT-PCR (4)
microRNA  (miRNA)   &   quantitative real-time RT-PCR (5)
microRNA   normalisation (7)


microRNA REVIEWS
How Do MicroRNAs Regulate Gene Expression?
Richard J. Jackson & Nancy Standart
Sci STKE. 2007(367): re1
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road,
Cambridge CB2 1GA, UK
Several thousand human genes, amounting to aboutone-third of the whole genome, are potential targetsfor regulation by the several hundred microRNAs(miRNAs) encoded in the genome. The regulationoccurs posttranscriptionally and involves the ~21-nucleotide miRNAinteracting with a target site in themRNAthat generally has imperfect complementarityto the miRNA. The target sites are almost invariablyin the 3′-untranslated region of the messenger RNA(mRNA), often in multiple copies. Metazoan miRNAswere previously thought to down-regulate proteinexpression by inhibiting target mRNAtranslation atsome stage after the translation initiation step, with-out much effect on mRNAabundance. However,recent studies have questioned these suppositions.With some targets, an increase in the rate of mRNAdegradation by the normal decay pathway con-tributes to the decrease in protein expression.miRNAs can also inhibit translation initiation, specif-ically the function of the cap-binding initiation factor,eIF4E. Repressed target mRNAs as well as miRNAsthemselves accumulate in cytoplasmic foci knownas P-bodies, where many enzymes involved in mRNAdegradation are concentrated. However, P-bodiesmay also serve as repositories for the temporary andreversible storage of untranslated mRNA, and reduc-ing the expression (knockdown) of several distinctP-body protein components can alleviate miRNA-mediated repression of gene expression.

MicroRNA: past and present
Yang Wang, Heidi M. Stricker, Deming Gou, Lin Liu
Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, 74078

Frontiers in Bioscience 12, 2316-2329, January 1, 2007
MicroRNAs (miRNAs) are ~22 nucleotide (nt) non-coding RNAs that participate in gene regulation.  MiRNAs confer their regulation at a post-transcriptional level, where they either cleave or repress translation of mRNAs.  Over 3000 identified mature miRNAs exist in species ranging from plants to humans, suggesting that they are ancient players in gene regulation.  A relatively small number of miRNAs have been experimentally tested for their function.  Of those tested, functions including cell differentiation, proliferation, apoptosis, anti-viral defense and cancer have been proposed.  Improved software programs are now able to predict the targets of miRNAs in a more efficient manner, thus facilitating the elucidation of miRNA function.  Furthermore, methods such as real-time PCR and microarray have been enhanced for studying miRNA expression.  Using these tools, scientists are able to discover novel functions for miRNAs.  It is possible that miRNAs will be revealed as having a role in virtually every aspect of gene regulation.  This review guides readers through the biogenesis of miRNAs, their mechanism of action on their target mRNAs, the functional outcomes of their action on mRNAs and the current techniques to investigate these processes.

Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
Filipowicz W, Bhattacharyya SN, Sonenberg N.
Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland. witold.filipowicz@fmi.ch
Nat Rev Genet. 2008 Feb;9(2): 102-114.
MicroRNAs constitute a large family of small, approximately 21-nucleotide-long, non-coding RNAs that have emerged as key post-transcriptional regulators of gene expression in metazoans and plants. In mammals, microRNAs are predicted to control the activity of approximately 30% of all protein-coding genes, and have been shown to participate in the regulation of almost every cellular process investigated so far. By base pairing to mRNAs, microRNAs mediate translational repression or mRNA degradation. This Review summarizes the current understanding of the mechanistic aspects of microRNA-induced repression of translation and discusses some of the controversies regarding different modes of microRNA function.

microRNAs in vertebrate physiology and human disease
Chang TC, Mendell JT.
The McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University
School of Medicine, Baltimore, Maryland, 21205, USA.
Annu Rev Genomics Hum Genet. 2007;8: 215-239.
Over the past five years, the importance of a diverse class of 18-24 nucleotide RNA molecules, known as microRNAs (miRNAs) has increasingly been recognized. These highly conserved RNAs regulate the stability and translational efficiency of complementary target messenger RNAs. The human genome is now predicted to encode nearly 1,000 miRNAs that likely regulate at least one third of all human transcripts. Despite rapid progress in miRNA discovery, the physiologic functions of only a small number have been definitively established. In this review, we discuss the principles of miRNA function that have emerged from the studies performed thus far in vertebrates. We also discuss known and potential roles for miRNAs in human disease states and discuss the influence of human genetic variation on miRNA-mediated regulation.

Illuminating the silence: understanding the structure and function of small RNAs
Tariq M. Rana
NATURE REVIEWS | MOLECULAR CELL BIOLOGY  VOLUME 8 | JANUARY 2007 | 23
RNA interference (RNAi) is triggered by double-stranded RNA helices that have been introduced exogenously into cells as small interfering (si)RNAs or that have been produced endogenously from small non-coding RNAs known as microRNAs (miRNAs). RNAi has become a standard experimental tool and its therapeutic potential is being aggressively harnessed. Understanding the structure and function of small RNAs, such as siRNAs and miRNAs, that trigger RNAi has shed light on the RNAi machinery. In particular, it has highlighted the assembly and function of the RNA-induced silencing complex (RISC), and has provided guidelines to efficiently silence genes for biological research and therapeutic applications of RNAi.

Everything you wanted to know about small RNA but were afraid to ask
Boyd SD.
Department of Pathology, Stanford University School of Medicine, Stanford, CA
94305-2297, USA.
Lab Invest. 2008 Jun;88(6): 569-578
MicroRNAs are a class of recently discovered small RNA molecules that regulate other genes in the human genome. Studies in human cells and model organisms have begun to reveal the mechanisms of microRNA activity, and the wide range of normal physiological functions they influence. Their alteration in pathologic statesfrom cancer to cardiovascular disease is also increasingly clear. A review of current evidence for the role of these molecules in human health and disease will be helpful to pathologists and medical researchers as the fascinating story of these small regulators continues to unfold.

The regulation of genes andgenomes by small RNAs
Victor Ambros & Xuemei Chen
Development 134, 1635-1641(2007)
A recent Keystone Symposium on ‘MicroRNAs and siRNAs:Biological Functions and Mechanisms’ was organized by DavidBartel and Shiv Grewal (and was held in conjunction with ‘RNAifor Target Validation and as a Therapeutic’, organized byStephen Friend and John Maraganore). The ‘MicroRNAs andsiRNAs’ meeting brought together scientists working on diversebiological aspects of small regulatory RNAs, includingmicroRNAs, small interfering RNAs (siRNAs) and Piwi-interactingRNAs (piRNAs and rasiRNAs). Among the themes discussed werethe diversity of small regulatory RNAs and their developmentalfunctions, their biogenesis, the identification of their regulatorytargets, their mechanisms of action, and their roles in theelaboration of multicellular complexity.

MicroRNAs in Gene Regulation: When the Smallest Governs It All
Ouellet DL, Perron MP, Gobeil LA, Plante P, Provost P.
J Biomed Biotechnol. 2006;2006(4): 69616.

Encoded by the genome of most eukaryotes examined so far, microRNAs (miRNAs) are small ~21-nucleotide (nt) noncoding RNAs (ncRNAs) derived from a biosynthetic cascade involving sequential processing steps executed by the ribonucleases (RNases) III Drosha and Dicer. Following their recent identification, miRNAs have rapidly taken the center stage as key regulators of gene expression. In this review, we will summarize our current knowledge of the miRNA biosynthetic pathway and its protein components, as well as the processes it regulates via miRNAs, which are known to exert a variety of biological functions in eukaryotes. Although the relative importance of miRNAs remains to be fully appreciated, deregulated protein expression resulting from either dysfunctional miRNA biogenesis or abnormal miRNA-based gene regulation may represent a key etiologic factor in several, as yet unidentified, diseases. Hence is our need to better understand the complexity of the basic mechanisms underlying miRNA biogenesis and function.

Clustering and conservation patterns of human microRNAs
Altuvia Y, Landgraf P, Lithwick G, Elefant N, Pfeffer S, Aravin A, Brownstein MJ, Tuschl T, Margalit H.
Department of Molecular Genetics and Biotechnology, Faculty of Medicine, The
Hebrew University PO Box 12272, Jerusalem 91120, Israel.
Nucleic Acids Res. 2005 May 12;33(8): 2697-2706
MicroRNAs (miRNAs) are approximately 22 nt-long non-coding RNA molecules, believed to play important roles in gene regulation. We present a comprehensive analysis of the conservation and clustering patterns of known miRNAs in human. We show that human miRNA gene clustering is significantly higher than expected at random. A total of 37% of the known human miRNA genes analyzed in this study appear in clusters of two or more with pairwise chromosomal distances of at most 3000 nt. Comparison of the miRNA sequences with their homologs in four other organisms reveals a typical conservation pattern, persistent throughout the clusters. Furthermore, we show enrichment in the typical conservation patterns and other miRNA-like properties in the vicinity of known miRNA genes, compared with random genomic regions. This may imply that additional, yet unknown, miRNAs reside in these regions, consistent with the current recognition that there are overlooked miRNAs. Indeed, by comparing our predictions with cloning results and with identified miRNA genes in other mammals, we corroborate the predictions of 18 additional human miRNA genes in the vicinity of the previously known ones. Our study raises the proportion of clustered human miRNAs that are <3000 nt apart to 42%. This suggests that the clustering of miRNA genes is higher than currently acknowledged, alluding to its evolutionary and functional implications.

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