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Results for “MicroRNAs”

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At least 19 recordsLinked to original sources
PubMed2006

Direct labeling microRNA with an electrocatalytic moiety and its application in ultrasensitive microRNA assays.

An ultrasensitive procedure for the detection of microRNA (miRNA) in total RNA is described in this work. The miRNA is directly labeled with a redox active and electrocatalytic moiety, Ru(PD)(2)Cl(2) (PD=1,10-phenanthroline-5,6-dione), through coordinative bonds with purine bases in the miRNA molecule. The excellent electrocatalytic activity of the Ru(PD)(2)Cl(2) towards the oxidation of hydrazine makes it possible to conduct ultrasensitive miRNA detection. Under optimized experimental conditions, the assay allows the detection of miRNAs in the range of 0.50-400 pM with a detection limit of 0.20 pM in 2.5 microl (0.50 amole). MicroRNA quantitation is therefore performed in as little as 10 ng of total RNA, providing a much-needed platform for miRNA expression analysis.

Biosensing Techniques↗
PubMed2007

Identification of differentially expressed microRNAs by microarray: a possible role for microRNA genes in pituitary adenomas.

MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by targeting mRNA. It has been demonstrated that miRNA expression is altered in many human cancers, suggesting that they may play a role in human neoplasia. To determine whether miRNA expression is altered in pituitary adenomas, we analyzed the entire miRNAome in 32 pituitary adenomas and in 6 normal pituitary samples by microarray and by Real-Time PCR. Here, we show that 30 miRNAs are differentially expressed between normal pituitary and pituitary adenomas. Moreover, 24 miRNAs were identified as a predictive signature of pituitary adenoma and 29 miRNAs were able to predict pituitary adenoma histotype. miRNA expression could differentiate micro- from macro-adenomas and treated from non-treated patient samples. Several of the identified miRNAs are involved in cell proliferation and apoptosis, suggesting that their deregulated expression may be involved in pituitary tumorigenesis. Predictive miRNAs could be potentially useful diagnostic markers, improving the classification of pituitary adenomas.

Adenoma↗
PubMed2007

Characterizing viral microRNAs and its application on identifying new microRNAs in viruses.

MicroRNAs (miRNAs) are a newly identified class of non-protein-coding small RNAs, which play important roles in multiple biological and metabolic processes at the post-transcriptional level by directly cleaving targeted mRNAs or inhibiting translation. The lengths of viral miRNA precursors vary from 60 to 119 with an average of 79 nucleotides, which was smaller than observed for plant or animal miRNAs. Viral miRNAs are less conserved than plant and animal miRNAs, suggesting that viral miRNAs may evolve rapidly. Uracil nucleotide was highly dominant in the first position of 5' mature miRNAs. Viral miRNAs had high minimal folding free energy index (MFEI, 0.9 +/- 0.1). Based on these features and the well-known characteristics of miRNAs, 20 new potential miRNAs were identified in viruses by using expressed sequence tag (EST) analysis and genomic sequence survey (GSS) analysis. A better understanding of viral miRNA functions will be useful to design new approaches for treating viruses, especially those viruses that can induce human, animal, and plant diseases.

Base Composition↗
PubMed2006

MicroRNA: microRNAs reach out into dendrites.

A recent study has shown that miR-134, a brain-specific microRNA, is present in dendrites where it represses the local synthesis of the protein kinase LimK1; this is a novel form of translational regulation in dendrites and may have important physiological implications.

Dendrites↗
PubMed2006

Rice embryogenic calli express a unique set of microRNAs, suggesting regulatory roles of microRNAs in plant post-embryogenic development.

In vitro cultured embryogenic callus was employed as a model to investigate microRNAs (miRNAs) associated with embryogenesis and post-embryonic development. Thirty-one miRNAs including 16 novel species were identified from a large number of small RNAs which were cloned from both differentiated and undifferentiated rice embryogenic calli. Four target genes of the miRNAs were further validated. A set of the miRNAs, including miR397 and miR156, exhibited intriguing expression patterns during the transition from undifferentiated to differentiated calli. By exploiting the correlations between the differential expression patterns of these miRNAs and their targets, the regulatory roles of the miRNAs on meristem maintenance and embryogenesis were indicated.

Base Sequence↗
PubMed2004

MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression.

MicroRNAs (miRNAs) are a class of short ( approximately 22-nt) noncoding RNA molecules that downregulate expression of their mRNA targets. Since their discovery as regulators of developmental timing in Caenorhabditis elegans, hundreds of miRNAs have been identified in both animals and plants. Here, we report a technique for visualizing detailed miRNA expression patterns in mouse embryos. We elucidate the tissue-specific expression of several miRNAs during embryogenesis, including two encoded by genes embedded in homeobox (Hox) clusters, miR-10a and miR-196a. These two miRNAs are expressed in patterns that are markedly reminiscent of those of Hox genes. Furthermore, miR-196a negatively regulates Hoxb8, indicating that its restricted expression pattern probably reflects a role in the patterning function of the Hox complex.

Animals↗
PubMed2005

The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation.

Understanding the molecular mechanisms that regulate cellular proliferation and differentiation is a central theme of developmental biology. MicroRNAs (miRNAs) are a class of regulatory RNAs of approximately 22 nucleotides that post-transcriptionally regulate gene expression. Increasing evidence points to the potential role of miRNAs in various biological processes. Here we show that miRNA-1 (miR-1) and miRNA-133 (miR-133), which are clustered on the same chromosomal loci, are transcribed together in a tissue-specific manner during development. miR-1 and miR-133 have distinct roles in modulating skeletal muscle proliferation and differentiation in cultured myoblasts in vitro and in Xenopus laevis embryos in vivo. miR-1 promotes myogenesis by targeting histone deacetylase 4 (HDAC4), a transcriptional repressor of muscle gene expression. By contrast, miR-133 enhances myoblast proliferation by repressing serum response factor (SRF). Our results show that two mature miRNAs, derived from the same miRNA polycistron and transcribed together, can carry out distinct biological functions. Together, our studies suggest a molecular mechanism in which miRNAs participate in transcriptional circuits that control skeletal muscle gene expression and embryonic development.

Animals↗
PubMed2004

MicroRNA control of PHABULOSA in leaf development: importance of pairing to the microRNA 5' region.

MicroRNAs (miRNAs) are approximately 22-nucleotide noncoding RNAs that can regulate gene expression by directing mRNA degradation or inhibiting productive translation. Dominant mutations in PHABULOSA (PHB) and PHAVOLUTA (PHV) map to a miR165/166 complementary site and impair miRNA-guided cleavage of these mRNAs in vitro. Here, we confirm that disrupted miRNA pairing, not changes in PHB protein sequence, causes the developmental defects in phb-d mutants. In planta, disrupting miRNA pairing near the center of the miRNA complementary site had far milder developmental consequences than more distal mismatches. These differences correlated with differences in miRNA-directed cleavage efficiency in vitro, where mismatch scanning revealed more tolerance for mismatches at the center and 3' end of the miRNA compared to mismatches to the miRNA 5' region. In this respect, miR165/166 resembles animal miRNAs in its pairing requirements. Pairing to the 5' portion of the small silencing RNA appears crucial regardless of the mode of post-transcriptional repression or whether it occurs in plants or animals, supporting a model in which this region of the silencing RNA nucleates pairing to its target.

Alleles↗
PubMed2006

MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy.

MicroRNAs (miRNAs) are a class of highly conserved, noncoding RNAs involved in posttranscriptional gene regulation. A small number of muscle-specific miRNAs have been identified and shown to have a role in myoblast proliferation and differentiation as well as embryonic muscle growth. The primary objective of the present study was to determine the expression level of the muscle-specific miRNAs in the soleus and plantaris muscles and whether their expression in the plantaris was altered in response to functional overload. Of the miRNAs examined, only miRNA-206 was differentially expressed between soleus and plantaris muscles, as reflected by the sevenfold higher expression in the soleus for both the primary miRNA (pri-miRNA) and mature miRNA (miR). Following 7 days of functional overload, transcript levels for both pri-miRNA-1-2 and pri-miRNA-133a-2 increased by approximately 2-fold, whereas pri-miRNA-206 levels were elevated 18.3-fold. In contrast, expression of miR-1 and miR-133a were downregulated by approximately 50% following overload. The discrepancy between pri-miRNA and miR expression following overload was not explained by a change in the expression of components of the miRNA biogenesis pathway, since Drosha and Exportin-5 transcript levels were significantly increased by 50% in response to functional overload, whereas Dicer expression remained unchanged. These results are the first to report alterations in expression of muscle-specific miRNAs in adult skeletal muscle and suggest miRNAs may have a role in the adaptation to functional overload.

Animals↗
PubMed2004

Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation.

BACKGROUND: The microRNAs (miRNAs) are an extensive class of small noncoding RNAs (18 to 25 nucleotides) with probable roles in the regulation of gene expression. In Caenorhabditis elegans, lin-4 and let-7 miRNAs control the timing of fate specification of neuronal and hypodermal cells during larval development. lin-4, let-7 and other miRNA genes are conserved in mammals, and their potential functions in mammalian development are under active study. RESULTS: In order to identify mammalian miRNAs that might function in development, we characterized the expression of 119 previously reported miRNAs in adult organs from mouse and human using northern blot analysis. Of these, 30 miRNAs were specifically expressed or greatly enriched in a particular organ (brain, lung, liver or skeletal muscle). This suggests organ- or tissue-specific functions for miRNAs. To test if any of the 66 brain-expressed miRNAs were present in neurons, embryonal carcinoma cells were treated with all-trans-retinoic acid to promote neuronal differentiation. A total of 19 brain-expressed miRNAs (including lin-4 and let-7 orthologs) were coordinately upregulated in both human and mouse embryonal carcinoma cells during neuronal differentiation. The mammalian ortholog of C. elegans lin-28, which is downregulated by lin-4 in worms via 3' untranslated region binding, was also repressed during neuronal differentiation of mammalian embryonal carcinoma cells. Mammalian lin-28 messenger RNAs contain conserved predicted binding sites in their 3' untranslated regions for neuron-expressed miR-125b (a lin-4 ortholog), let-7a, and miR-218. CONCLUSIONS: The identification of a subset of brain-expressed miRNAs whose expression behavior is conserved in both mouse and human differentiating neurons implicates these miRNAs in mammalian neuronal development or function.

Adult↗
PubMed2003

A microRNA array reveals extensive regulation of microRNAs during brain development.

Several hundred microRNAs (miRNAs) have recently been cloned from a wide range of organisms across phylogeny. Despite the high degree of conservation of miRNAs, their functions in general, and in mammals particularly, are just beginning to be defined. Here we show that an oligonucleotide DNA array can be successfully used for the simultaneous analysis of miRNA expression profiles from tissues or cells. From a subset of miRNAs expressed in the brain we designed an oligonucleotide array spotted with probes specific for 44 mature miRNAs. These arrays demonstrated precise regulation of miRNA expression at mammalian brain developmental epochs. About 20% of the probed miRNAs changed significantly in their expression during normal brain development, and two of them, miR-9 and miR-131, were dysregulated in presenilin-1 null mice exhibiting severe brain developmental defects. Transcripts with regulated expression patterns on the arrays were validated by Northern blots. Additionally, a bioinformatic analysis of developmentally regulated miRNAs suggested potential mRNA targets. The arrays also revealed miRNAs distributed to translating polyribosomes in primary neurons where they are likely to modulate translation. Therefore, oligonucleotide arrays provide a new tool for studying miRNA expression in a variety of biological and pathobiological settings. Creating clusters of coexpressed miRNAs will contribute to understanding their regulation, functions, and discovery of mRNA targets.

Animals↗
PubMed2006

MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers.

MicroRNAs (miRNAs) are endogenously expressed RNAs 18-24 nucleotides in length that regulate gene expression through translational repression by binding to a target mRNA. It is thought that the expression level of miRNAs, which act like antioncogenes, is frequently reduced in cancers because of chromosome deletion and epigenetic changes. Since the processing of miRNAs has been characterized to be enzymatic in nature, the expression levels of miRNAs are closely associated with the activity and levels of such enzymes. Here, we found that miRNA 143 and 145 expression levels were extremely reduced in colon cancer cells and commonly in the other kinds of cancer cells tested. The transfection of each precursor miRNA into the cells demonstrated a significant growth inhibition in human colon cancer DLD-1 and SW480 cells, and ERK5 was determined to be the target gene of miRNA 143. Since the presence of genomic loci of the miRNAs was confirmed by PCR in the cell lines and the precursor miRNAs exhibited a growth inhibitory effect in DLD-1 and SW480 cells, the early processes such as transcription and enzymatic modification from primary miRNAs to precursor miRNAs seemed to be commonly disturbed. These findings indicate that the miRNAs 143 and 145 could become good tumor markers and provide an important clue in the study of the mechanism of oncogenesis involving miRNAs.

Cell Line, Tumor↗
PubMed2004

Microarray analysis of microRNA expression in the developing mammalian brain.

BACKGROUND: MicroRNAs are a large new class of tiny regulatory RNAs found in nematodes, plants, insects and mammals. MicroRNAs are thought to act as post-transcriptional modulators of gene expression. In invertebrates microRNAs have been implicated as regulators of developmental timing, neuronal differentiation, cell proliferation, programmed cell death and fat metabolism. Little is known about the roles of microRNAs in mammals. RESULTS: We isolated 18-26 nucleotide RNAs from developing rat and monkey brains. From the sequences of these RNAs and the sequences of the rat and human genomes we determined which of these small RNAs are likely to have derived from stem-loop precursors typical of microRNAs. Next, we developed a microarray technology suitable for detecting microRNAs and printed a microRNA microarray representing 138 mammalian microRNAs corresponding to the sequences of the microRNAs we cloned as well as to other known microRNAs. We used this microarray to determine the profile of microRNAs expressed in the developing mouse brain. We observed a temporal wave of expression of microRNAs, suggesting that microRNAs play important roles in the development of the mammalian brain. CONCLUSION: We describe a microarray technology that can be used to analyze the expression of microRNAs and of other small RNAs. MicroRNA microarrays offer a new tool that should facilitate studies of the biological roles of microRNAs. We used this method to determine the microRNA expression profile during mouse brain development and observed a temporal wave of gene expression of sequential classes of microRNAs.

Animals↗
PubMed2005

microRNA target predictions across seven Drosophila species and comparison to mammalian targets.

microRNAs are small noncoding genes that regulate the protein production of genes by binding to partially complementary sites in the mRNAs of targeted genes. Here, using our algorithm PicTar, we exploit cross-species comparisons to predict, on average, 54 targeted genes per microRNA above noise in Drosophila melanogaster. Analysis of the functional annotation of target genes furthermore suggests specific biological functions for many microRNAs. We also predict combinatorial targets for clustered microRNAs and find that some clustered microRNAs are likely to coordinately regulate target genes. Furthermore, we compare microRNA regulation between insects and vertebrates. We find that the widespread extent of gene regulation by microRNAs is comparable between flies and mammals but that certain microRNAs may function in clade-specific modes of gene regulation. One of these microRNAs (miR-210) is predicted to contribute to the regulation of fly oogenesis. We also list specific regulatory relationships that appear to be conserved between flies and mammals. Our findings provide the most extensive microRNA target predictions in Drosophila to date, suggest specific functional roles for most microRNAs, indicate the existence of coordinate gene regulation executed by clustered microRNAs, and shed light on the evolution of microRNA function across large evolutionary distances. All predictions are freely accessible at our searchable Web site http://pictar.bio.nyu.edu.

Journal Article↗
PubMed2004

A population-based statistical approach identifies parameters characteristic of human microRNA-mRNA interactions.

BACKGROUND: MicroRNAs are approximately 17-24 nt. noncoding RNAs found in all eukaryotes that degrade messenger RNAs via RNA interference (if they bind in a perfect or near-perfect complementarity to the target mRNA), or arrest translation (if the binding is imperfect). Several microRNA targets have been identified in lower organisms, but only one mammalian microRNA target has yet been validated experimentally. RESULTS: We carried out a population-wide statistical analysis of how human microRNAs interact complementarily with human mRNAs, looking for characteristics that differ significantly as compared with scrambled control sequences. These characteristics were used to identify a set of 71 outlier mRNAs unlikely to have been hit by chance. Unlike the case in C. elegans and Drosophila, many human microRNAs exhibited long exact matches (10 or more bases in a row), up to and including perfect target complementarity. Human microRNAs hit outlier mRNAs within the protein coding region about 2/3 of the time. And, the stretches of perfect complementarity within microRNA hits onto outlier mRNAs were not biased near the 5'-end of the microRNA. In several cases, an individual microRNA hit multiple mRNAs that belonged to the same functional class. CONCLUSIONS: The analysis supports the notion that sequence complementarity is the basis by which microRNAs recognize their biological targets, but raises the possibility that human microRNA-mRNA target interactions follow different rules than have been previously characterized in Drosophila and C. elegans.

Computational Biology↗
PubMed2005

A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia.

BACKGROUND: MicroRNA expression profiles can be used to distinguish normal B cells from malignant B cells in patients with chronic lymphocytic leukemia (CLL). We investigated whether microRNA profiles are associated with known prognostic factors in CLL. METHODS: We evaluated the microRNA expression profiles of 94 samples of CLL cells for which the level of expression of 70-kD zeta-associated protein (ZAP-70), the mutational status of the rearranged immunoglobulin heavy-chain variable-region (IgV(H) ) gene, and the time from diagnosis to initial treatment were known. We also investigated the genomic sequence of 42 microRNA genes to identify abnormalities. RESULTS: A unique microRNA expression signature composed of 13 genes (of 190 analyzed) differentiated cases of CLL with low levels of ZAP-70 expression from those with high levels and cases with unmutated IgV(H) from those with mutated IgV(H) . The same microRNA signature was also associated with the presence or absence of disease progression. We also identified a germ-line mutation in the miR-16-1-miR-15a primary precursor, which caused low levels of microRNA expression in vitro and in vivo and was associated with deletion of the normal allele. Germ-line or somatic mutations were found in 5 of 42 sequenced microRNAs in 11 of 75 patients with CLL, but no such mutations were found in 160 subjects without cancer (P<0.001). CONCLUSIONS: A unique microRNA signature is associated with prognostic factors and disease progression in CLL. Mutations in microRNA transcripts are common and may have functional importance.

Disease Progression↗
PubMed2007

Expression profiling identifies microRNA signature in pancreatic cancer.

microRNAs are functional, 22 nt, noncoding RNAs that negatively regulate gene expression. Disturbance of microRNA expression may play a role in the initiation and progression of certain diseases. A microRNA expression signature has been identified that is associated with pancreatic cancer. This has been accomplished with the application of real-time PCR profiling of over 200 microRNA precursors on specimens of human pancreatic adenocarcinoma, paired benign tissue, normal pancreas, chronic pancreatitis and nine pancreatic cancer cell lines. Hierarchical clustering was able to distinguish tumor from normal pancreas, pancreatitis and cell lines. The PAM algorithm correctly classified 28 of 28 tumors, 6 of 6 normal pancreas and 11 of 15 adjacent benign tissues. One hundred microRNA precursors were aberrantly expressed in pancreatic cancer or desmoplasia (p < 0.01), including microRNAs previously reported as differentially expressed in other human cancers (miR-155, miR-21, miR-221 and miR-222) as well as those not previously reported in cancer (miR-376a and miR-301). Most of the top aberrantly expressed miRNAs displayed increased expression in the tumor. Expression of the active, mature microRNA was validated using a real-time PCR assay to quantify the mature microRNA and Northern blotting. Reverse transcription in situ PCR showed that three of the top differentially expressed miRNAs (miR-221, -376a and -301) were localized to tumor cells and not to stroma or normal acini or ducts. Aberrant microRNA expression may offer new clues to pancreatic tumorigenesis and may provide diagnostic biomarkers for pancreatic adenocarcinoma.

Adenocarcinoma↗