MicroRNAs and cancer.
Journal - Journal of internal medicine (England )
The Nobel Prize in Medicine and Physiology was awarded to the RNA interference (RNAi) field in 2006 because of the huge therapeutic potential this technique harbours. However, the RNAi technology is based on a natural mechanism that utilizes short noncoding RNA molecules (microRNAs) to regulate gene expression. This paper reviews our current knowledge about microRNAs focusing on their involvement in cancer and their potential as diagnostics and therapeutics.
|ISSN : ||1365-2796|
|Mesh Heading : ||Animals Apoptosis Cell Proliferation Female Gene Silencing Humans Male MicroRNAs Neoplasms RNA Interference diagnosis therapy physiology|
|Mesh Heading Relevant : ||genetics physiology genetics|
Identification of genes targeted by microRNAs.
Journal - Biochemical Society transactions (England )
miRNAs (microRNAs) are recently discovered regulators of gene expression. They target mRNAs that contain partially complementary sites to the miRNA. The level of complementarity is different between target site-miRNA pairs, and finding target genes has proved to be a bigger challenge than expected. The present paper reviews the different approaches to predict and experimentally identify genes targeted by miRNAs.
|ISSN : ||1470-8752|
|Mesh Heading : ||Animals Down-Regulation Humans MicroRNAs RNA-Induced Silencing Complex genetics metabolism|
|Mesh Heading Relevant : ||Genes genetics|
Short RNAs in environmental adaptation.
Journal - Proceedings. Biological sciences / The Royal Society (England )
Non-coding small RNAs (19-24 nucleotide long) have recently been recognized as the important regulator of gene expression in both plants and animals. Several classes of endogenous short RNAs have partial or near perfect complementarity to mRNAs and a protein complex is guided by short RNAs to target mRNAs. The targeted mRNA is either cleaved or its translation is suppressed. Initially, short RNAs were believed to primarily regulate the normal development of plants and animals, but recent advances implicate short RNAs in environmental adaptation.
|ISSN : ||0962-8452|
|Mesh Heading : ||Acclimatization Animals MicroRNAs Plants RNA Interference RNA, Messenger RNA, Small Interfering genetics metabolism|
|Mesh Heading Relevant : ||genetics physiology physiology physiology|
MicroRNAs and the hallmarks of cancer.
Journal - Oncogene (England )
It has become clear that particular microRNAs (miRNAs) function either as tumour suppressors or oncogenes, whose loss or overexpression, respectively, has diagnostic and prognostic significance. In several cases, miRNAs have been shown to affect target genes that are involved in the control of cell proliferation and apoptosis. However, malignant tumours display additional traits beyond the acquisition of enhanced growth potential and decreased cell death. Malignant disease is associated with altered tumour-host interactions leading to sustained angiogenesis and the ability to invade and metastasize. It is possible that miRNAs may act as master regulators of these aspects of tumour biology. Bioinformatic analysis of putative miRNA binding sites has indicated several novel potential gene targets of cancer-associated miRNAs that function in aspects of cell adhesion, neovascularization and tissue invasion. Among others, we speculate that miRNAs may find new roles in the regulation of E-cadherin, integrin alphavbeta3, hypoxia-inducible factor-1alpha, syndecan-1, lysyl oxidase, adamalysin metalloproteinase-17, tissue inhibitors of metalloproteinase-3, c-Met and CXCR-4 that underpin the tissue architectural changes associated with malignancy.
|ISSN : ||0950-9232|
|Mesh Heading : ||Animals Forecasting Genes, Tumor Suppressor Humans MicroRNAs Neoplasms Oncogenes genetics|
|Mesh Heading Relevant : ||genetics genetics|
High-throughput sequencing of Medicago truncatula short RNAs identifies eight new miRNA families
Journal - BMC Genomics
BackgroundHigh-throughput sequencing technology is capable to identify novel short RNAs in plant species. We used Solexa sequencing to find new microRNAs in one of the model legume species, barrel medic (Medicago truncatula).Results3,948,871 reads were obtained from two separate short RNA libraries generated from total RNA extracted from M. truncatula leaves, representing 1,563,959 distinct sequences. 2,168,937 reads were mapped to the available M. truncatula genome corresponding to 619,175 distinct sequences. 174,504 reads representing 25 conserved miRNA families showed perfect matches to known miRNAs. We also identified 26 novel miRNA candidates that were potentially generated from 32 loci. Nine of these loci produced eight distinct sequences, for which the miRNA* sequences were also sequenced. These sequences were not described in other plant species and accumulation of these eight novel miRNAs was confirmed by Northern blot analysis. Potential target genes were predicted for most conserved and novel miRNAs.ConclusionDeep sequencing of short RNAs from M. truncatula leaves identified eight new miRNAs indicating that specific miRNAs exist in legume species.
The p122 Subunit of Tobacco Mosaic Virus Replicase Is a Potent Silencing Suppressor and Compromises both Small Interfering RNA- and MicroRNA-Mediated Pathways
Journal - Journal of Virology
One of the functions of RNA silencing in plants is to defend against molecular parasites, such as viruses, retrotransposons, and transgenes. Plant viruses are inducers, as well as targets, of RNA silencing-based antiviral defense. Replication intermediates or folded viral RNAs activate RNA silencing, generating small interfering RNAs (siRNAs), which are the key players in the antiviral response. Viruses are able to counteract RNA silencing by expressing silencing-suppressor proteins. It has been shown that many of the identified silencing-suppressor proteins bind long double-stranded RNA or siRNAs and thereby prevent assembly of the silencing effector complexes. In this study, we show that the 122-kDa replicase subunit (p122) of crucifer-infecting Tobacco mosaic virus (cr-TMV) is a potent silencing-suppressor protein. We found that the p122 protein preferentially binds to double-stranded 21-nucleotide (nt) siRNA and microRNA (miRNA) intermediates with 2-nt 3' overhangs inhibiting the incorporation of siRNA and miRNA into silencing-related complexes (e.g., RNA-induced silencing complex [RISC]) both in vitro and in planta but cannot interfere with previously programmed RISCs. In addition, our results also suggest that the virus infection and/or sequestration of the siRNA and miRNA molecules by p122 enhances miRNA accumulation despite preventing its methylation. However, the p122 silencing suppressor does not prevent the methylation of certain miRNAs in hst-15 mutants, in which the nuclear export of miRNAs is compromised.
Embryonic temperature affects muscle fibre recruitment in adult zebrafish: genome-wide changes in gene and microRNA expression associated with the transition from hyperplastic to hypertrophic growth phenotypes
Journal - Journal of Experimental Biology
Accepted for publication 12 March 2009.
We investigated the effects of embryonic temperature (ET) treatments(22,
26 and 31°C) on the life-time recruitment of fast myotomalmuscle fibres
in zebrafish Danio rerio L. reared at 26/27°Cfrom hatching. Fast
muscle fibres were produced until 25 mmtotal length (TL) at 22°C ET, 28
mm TL at 26°C ET and23 mm TL at 31°C ET. The final fibre number (FFN)
showedan optimum at 26°C ET (3600) and was 19% and 14% higherthan for
the 22°C ET (3000) and 31°C ET (3100) treatments,respectively.
Further growth to the maximum TL of 48 mm onlyinvolved fibre
hypertrophy. Microarray experiments were usedto determine global changes in
microRNA (miRNA) and mRNA expressionassociated with the transition from the
hyperplasic myotube-producingphenotype (M+, 10–12 mm TL) to
the hypertrophic growthphenotype (M–, 28–31 mm TL) in
fish reared at 26–27°Cover the whole life-cycle. The expression of
miRNAs and mRNAsobtained from microarray experiments was validated by
northernblotting and real-time qPCR in independent samples of fish withthe
M+ and M– phenotype. Fourteen down-regulated and
15up-regulated miRNAs were identified in the M– phenotype
togetherwith 34 down-regulated and 30 up-regulated mRNAs (>2-fold;
P<0.05).The two most abundant categories of down-regulated genes
inthe M– phenotype encoded contractile proteins (23.5%)and
sarcomeric structural/cytoskeletal proteins (14.7%). Incontrast, the most
highly represented up-regulated transcriptsin the M–
phenotype were energy metabolism (26.7%) andimmune-related (20.0%) genes. The
latter were mostly involvedin cell–cell interactions and cytokine
pathways and includedß-2-microglobulin precursor (b2m), an
orthologue of complementcomponent 4, invariant chain-like protein 1
(iclp), CD9 antigen-like(cd9l), and tyrosine kinase,
non-receptor (tnk2). Five myosinheavy chain genes that were
down-regulated in the M– phenotypeformed part of a tandem
repeat on chromosome 5 and were shownby in situ hybridisation to be
specifically expressed in nascentmyofibres. Seven up-regulated miRNAs in the
M– phenotypeshowed reciprocal expression with seven mRNA
targets identifiedin miRBase Targets version 5
includingasporin (aspn) which was the target for four miRNAs. Eleven
down-regulatedmiRNAs in the M– phenotype had predicted
targets for sevenup-regulated genes, including dre-miR-181c which had five
predictedmRNA targets. These results provide evidence that miRNAs playa role
in regulating the transition from the M+ to the M–
phenotypeand identify some of the genes and regulatory interactions
|Keywords : ||Danio rerio • microRNA • developmental plasticity • temperature • muscle growth • muscle hyperplasia • gene expression • myosin heavy chains • ß-2-microglobulin|