SEARCH · PubMed Health

Results for “MicroRNA”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources

PubMed2005

Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets.

We predict regulatory targets of vertebrate microRNAs (miRNAs) by identifying mRNAs with conserved complementarity to the seed (nucleotides 2-7) of the miRNA. An overrepresentation of conserved adenosines flanking the seed complementary sites in mRNAs indicates that primary sequence determinants can supplement base pairing to specify miRNA target recognition. In a four-genome analysis of 3' UTRs, approximately 13,000 regulatory relationships were detected above the estimate of false-positive predictions, thereby implicating as miRNA targets more than 5300 human genes, which represented 30% of our gene set. Targeting was also detected in open reading frames. In sum, well over one third of human genes appear to be conserved miRNA targets.

3' Untranslated Regions↗

PubMed2005

Involvement of microRNA in AU-rich element-mediated mRNA instability.

AU-rich elements (AREs) in the 3' untranslated region (UTR) of unstable mRNAs dictate their degradation. An RNAi-based screen performed in Drosophila S2 cells has revealed that Dicer1, Argonaute1 (Ago1) and Ago2, components involved in microRNA (miRNA) processing and function, are required for the rapid decay of mRNA containing AREs of tumor necrosis factor-alpha. The requirement for Dicer in the instability of ARE-containing mRNA (ARE-RNA) was confirmed in HeLa cells. We further observed that miR16, a human miRNA containing an UAAAUAUU sequence that is complementary to the ARE sequence, is required for ARE-RNA turnover. The role of miR16 in ARE-RNA decay is sequence-specific and requires the ARE binding protein tristetraprolin (TTP). TTP does not directly bind to miR16 but interacts through association with Ago/eiF2C family members to complex with miR16 and assists in the targeting of ARE. miRNA targeting of ARE, therefore, appears to be an essential step in ARE-mediated mRNA degradation.

3' Untranslated Regions↗

PubMed2005

RAS is regulated by the let-7 microRNA family.

MicroRNAs (miRNAs) are regulatory RNAs found in multicellular eukaryotes, including humans, where they are implicated in cancer. The let-7 miRNA times seam cell terminal differentiation in C. elegans. Here we show that the let-7 family negatively regulates let-60/RAS. Loss of let-60/RAS suppresses let-7, and the let-60/RAS 3'UTR contains multiple let-7 complementary sites (LCSs), restricting reporter gene expression in a let-7-dependent manner. mir-84, a let-7 family member, is largely absent in vulval precursor cell P6.p at the time that let-60/RAS specifies the 1 degrees vulval fate in that cell, and mir-84 overexpression suppresses the multivulva phenotype of activating let-60/RAS mutations. The 3'UTRs of the human RAS genes contain multiple LCSs, allowing let-7 to regulate RAS expression. let-7 expression is lower in lung tumors than in normal lung tissue, while RAS protein is significantly higher in lung tumors, providing a possible mechanism for let-7 in cancer.

3' Untranslated Regions↗

PubMed2005

microRNA-directed phasing during trans-acting siRNA biogenesis in plants.

Plants and animals use small RNAs (microRNAs [miRNAs] and siRNAs) as guides for posttranscriptional and epigenetic regulation. In plants, miRNAs and trans-acting (ta) siRNAs form through distinct biogenesis pathways, although they both interact with target transcripts and guide cleavage. An integrated approach to identify targets of Arabidopsis thaliana miRNAs and ta-siRNAs revealed several new classes of small RNA-regulated genes, including conventional genes such as Argonaute2 and an E2-ubiquitin conjugating enzyme. Surprisingly, five ta-siRNA-generating transcripts were identified as targets of miR173 or miR390. Rather than functioning as negative regulators, miR173- and miR390-guided cleavage was shown to set the 21-nucleotide phase for ta-siRNA precursor processing. These data support a model in which miRNA-guided formation of a 5' or 3' terminus within pre-ta-siRNA transcripts, followed by RDR6-dependent formation of dsRNA and Dicer-like processing, yields phased ta-siRNAs that negatively regulate other genes.

Arabidopsis↗

PubMed2005

A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis.

MicroRNAs play important roles in cell differentiation by acting as translational inhibitors of specific target genes. Here we show that human granulocytic differentiation is controlled by a regulatory circuitry involving miR-223 and two transcriptional factors, NFI-A and C/EBPalpha. The two factors compete for binding to the miR-223 promoter: NFI-A maintains miR-223 at low levels, whereas its replacement by C/EBPalpha, following retinoic acid (RA)-induced differentiation, upregulates miR-223 expression. The competition by C/EBPalpha and the granulocytic differentiation are favored by a negative-feedback loop in which miR-223 represses NFI-A translation. In line with this, both RNAi against NFI-A and ectopic expression of miR-223 in acute promyelocytic leukemia (APL) cells enhance differentiation, whereas miR-223 knockdown inhibits the differentiation response to RA. Altogether, our data indicate that miR-223 plays a crucial role during granulopoiesis and point to the NFI-A repression as an important molecular pathway mediating gene reprogramming in this cell lineage.

Binding Sites↗

PubMed2005

Human RISC couples microRNA biogenesis and posttranscriptional gene silencing.

RNA interference is implemented through the action of the RNA-induced silencing complex (RISC). Although Argonaute2 has been identified as the catalytic center of RISC, the RISC polypeptide composition and assembly using short interfering RNA (siRNA) duplexes has remained elusive. Here we show that RISC is composed of Dicer, the double-stranded RNA binding protein TRBP, and Argonaute2. We demonstrate that this complex can cleave target RNA using precursor microRNA (pre-miRNA) hairpin as the source of siRNA. Although RISC can also utilize duplex siRNA, it displays a nearly 10-fold greater activity using the pre-miRNA Dicer substrate. RISC distinguishes the guide strand of the siRNA from the passenger strand and specifically incorporates the guide strand. Importantly, ATP is not required for miRNA processing, RISC assembly, or multiple rounds of target-RNA cleavage. These results define the composition of RISC and demonstrate that miRNA processing and target-RNA cleavage are coupled.

Adenosine Triphosphate↗

PubMed2005

A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye.

A critical question about signal transduction is how weak or transient activation of signaling pathways achieves a robust and long-term switch in gene expression. We report that a microRNA is part of a mechanism that makes cells sensitive to signals in the Drosophila eye. Expression of miR-7 is activated in cells as they begin differentiating into photoreceptors. This is dependent on EGF receptor (EGFR) signaling that triggers ERK-mediated degradation of the transcription factor Yan. In nonstimulated cells, Yan represses miR-7 transcription, whereas miR-7 RNA represses Yan protein expression in photoreceptors, by binding to sequences within its mRNA 3'UTR. We propose that reciprocal negative feedback between Yan and miR-7 ensures mutually exclusive expression, with Yan in progenitor cells and miR-7 in photoreceptor cells. Expression is switched when EGFR signaling transiently triggers Yan degradation. This two-tiered mechanism explains how signal transduction activity can robustly generate a stable change in gene-expression patterns.

Animals↗

PubMed2006

The Hippo pathway regulates the bantam microRNA to control cell proliferation and apoptosis in Drosophila.

The Hippo signaling pathway acts upon the Yorkie transcriptional activator to control tissue growth in Drosophila. Activated Yorkie drives growth by stimulating cell proliferation and inhibiting apoptosis, but how it achieves this is not understood. Yorkie is known to activate Cyclin E (CycE) and the apoptosis inhibitor DIAP1. However, overexpression of these targets is not sufficient to cause tissue overgrowth. Here we show that Yorkie also activates expression of the bantam microRNA, a known regulator of both proliferation and apoptosis. bantam overexpression mimics Yorkie activation while loss of bantam function slows the rate of cell proliferation. bantam is necessary for Yorkie-induced overproliferation and bantam overexpression is sufficient to rescue survival and proliferation of yorkie mutant cells. Finally, we show that bantam levels are regulated during both developmentally programmed proliferation arrest and apoptosis. In summary, the results show that the Hippo pathway regulates expression of bantam to control tissue growth in Drosophila.

Animals↗

PubMed2006

Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans.

We sequenced approximately 400,000 small RNAs from Caenorhabditis elegans. Another 18 microRNA (miRNA) genes were identified, thereby extending to 112 our tally of confidently identified miRNA genes in C. elegans. Also observed were thousands of endogenous siRNAs generated by RNA-directed RNA polymerases acting preferentially on transcripts associated with spermatogenesis and transposons. In addition, a third class of nematode small RNAs, called 21U-RNAs, was discovered. 21U-RNAs are precisely 21 nucleotides long, begin with a uridine 5'-monophosphate but are diverse in their remaining 20 nucleotides, and appear modified at their 3'-terminal ribose. 21U-RNAs originate from more than 5700 genomic loci dispersed in two broad regions of chromosome IV-primarily between protein-coding genes or within their introns. These loci share a large upstream motif that enables accurate prediction of additional 21U-RNAs. The motif is conserved in other nematodes, presumably because of its importance for producing these diverse, autonomously expressed, small RNAs (dasRNAs).

Animals↗

PubMed2006

MicroRNAs: a new class of regulatory genes affecting metabolism.

MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene expression by binding to target mRNAs, which leads to reduced protein synthesis and sometimes decreased steady-state mRNA levels. Although hundreds of miRNAs have been identified, much less is known about their biological function. Several studies have provided evidence that miRNAs affect pathways that are fundamental for metabolic control in higher organisms such as adipocyte and skeletal muscle differentiation. Furthermore, some miRNAs have been implicated in lipid, amino acid, and glucose homeostasis. These studies open the possibility that miRNAs may contribute to common metabolic diseases and point to novel therapeutic opportunities based on targeting of miRNAs.

Animals↗

PubMed2006

Computational identification of microRNAs and their targets.

MicroRNAs (miRNAs) are one class of newly identified riboregulators of gene expression in many eukaryotic organisms. They play important roles in multiple biological and metabolic processes, including developmental timing, signal transduction, cell maintenance and differentiation, diseases and cancers. miRNAs regulate gene expression at the posttranscriptional level by directly cleaving targeted mRNAs or repressing translation. Although the founding members of miRNAs were discovered by genetic screening approaches, experimental approaches were limited by their low efficiency, time consuming, and high cost. As an alternative, computational approaches were developed. Computational approaches for identifying miRNAs are based on the following major characteristics of miRNAs: hairpin-shaped secondary structures, high conservation for some miRNAs, and high minimal folding free energy index (MFEI). Computational approaches also play an important role in identifying miRNA targets. A majority of known miRNAs and their targets were identified by computational approaches. Several web-based or non-web-based computer software programs are publicly available for predicting miRNAs and their targets.

Animals↗

PubMed2006

A trace of silence: memory and microRNA at the synapse.

Identifying the neural circuits that mediate particular behaviors and uncovering their plasticity is an endeavor at the heart of neuroscience. This effort is allied with the elucidation of plasticity mechanisms, because the molecular determinants of plasticity can be markers for the neurons and synapses that are modified by experience. Of particular interest is protein synthesis localized to the synapse, which might establish and maintain the stable modification of neuronal properties, including the pattern and strength of synaptic connections. Recent studies reveal that microRNAs and the RISC pathway regulate synaptic protein synthesis. Is synaptic activity of the RISC pathway a molecular signature of memory?

Animals↗

PubMed2006

Sweating the small stuff: microRNA discovery in plants.

The class of small RNAs known as microRNAs (miRNAs) has a demonstrated role in the negative regulation of gene expression in both plants and animals. These small molecules have been shown to play a critical role in a wide range of developmental and physiological pathways. Although hundreds of different miRNAs have now been identified using cloning and computational approaches, characterization of their targets and biological roles has been more limited. New sequencing technologies promise to accelerate the sequencing of small RNAs and additional genetic and genomic strategies are being applied to assess their regulatory function on RNA targets. These technologies will enable the identification of large numbers of small RNAs from diverse species, and comparative genomics approaches based on these data are likely to identify additional miRNAs. Combined with bioinformatics and experimental approaches to separate miRNAs from short-interfering RNAs (siRNAs), the pace of miRNA discovery is likely to accelerate, leading to an improved understanding of miRNA function and biological significance.

MicroRNAs↗

PubMed2003

MicroRNAs: a role in plant development.

MicroRNAs are known to regulate development in Caenorhabditis elegans by translational repression of target genes. MiRNAs have now been shown to regulate developmental processes in plants, using both translational repression and cleavage of the target gene's RNA transcript.

Gene Expression Regulation, Plant↗

PubMed2004

The nuclear dsRNA binding protein HYL1 is required for microRNA accumulation and plant development, but not posttranscriptional transgene silencing.

MicroRNAs (miRNAs) are 21-24 nucleotides long molecules processed from imperfect double-stranded RNAs (dsRNAs). They regulate gene expression by targeting complementary mRNA for cleavage or interfering with their translation. In Arabidopsis, point mutations in or short truncations of the nuclear DICER-LIKE1 (DCL1) or HEN1 protein reduce miRNA accumulation and increase uncleaved target mRNAs accumulation, resulting in developmental abnormalities. Here, we show that miRNA accumulation also depends on the activity of HYL1, a nuclear dsRNA binding protein. hyl1 mutants exhibit developmental defects overlapping with that of dcl1 and hen1 mutants, suggesting that DCL1, HEN1, and HYL1 act together in the nucleus. We validate additional target mRNAs and show that reduced miRNA accumulation in hyl1 correlates with an increased accumulation of uncleaved target mRNAs, including meristem- and auxin-related genes, providing clues for the developmental abnormalities of hyl1 and for the previous identification of hyl1 as a mutant with altered responses to phytohormones. Lastly, we show that posttranscriptional transgene silencing occurs in hyl1, suggesting that HYL1 has specialized function in the plant miRNA pathway, whereas the HYL1-related RDE-4 and R2D2 proteins associate with DICER in the cytoplasm and act in the RNAi pathway in C. elegans and Drosophila, respectively.

Arabidopsis↗

PubMed2005

The early extra petals1 mutant uncovers a role for microRNA miR164c in regulating petal number in Arabidopsis.

BACKGROUND: MicroRNAs (miRNAs) are small 20-25 nucleotide non-protein-coding RNAs that negatively regulate expression of genes in many organisms, ranging from plants to humans. The MIR164 family of miRNAs in Arabidopsis consists of three members that share sequence complementarity to transcripts of NAC family transcription factors, including CUP-SHAPED COTYLEDON1 (CUC1) and CUC2. CUC1 and CUC2 are redundantly required for the formation of boundaries between organ primordia. The analysis of transgenic plants that either overexpress miR164a or miR164b or express a miRNA-resistant version of CUC1 or CUC2 has shown that miRNA regulation of CUC1 and CUC2 is necessary for normal flower development. A loss-of-function allele of MIR164b did not result in a mutant phenotype, possibly because of functional redundancy among the three members of the MIR164 family. RESULTS: In this study, we describe the characterization of the early extra petals1 (eep1) Arabidopsis mutant, whose predominant phenotype is the formation of extra petals in early-arising flowers. We demonstrate that eep1 is a loss-of-function allele of MIR164c, one of three known members of the MIR164 family. Our analyses of miR164c function and eep1 mir164b double mutants reveal that miR164c controls petal number in a nonredundant manner by regulating the transcript accumulation of the transcription factors CUC1 and CUC2. CONCLUSIONS: The data presented in this study indicate that closely related miRNA family members that are predicted to target the same set of genes can have different functions during development, possibly because of nonoverlapping expression patterns.

Arabidopsis↗

PubMed2005

MicroRNAs: all gone and then what?

MicroRNAs are abundant gene regulatory factors whose function in animal development and homeostasis is poorly understood. A new study reports the genetic elimination of miRNA function on a full genomic scale and identifies a subfamily of miRNAs involved in brain morphogenesis.

Animals↗

PubMedDate not supplied

MicroRNAs: Small regulators with a big impact.

MicroRNAs (miRNA) are non-coding small (approximately 22nt) RNAs that regulate diverse physiological and developmental processes. In animals, they regulate target genes by binding imperfectly to 3'UTR sequences in mRNAs and attenuate translation. There are hundreds of miRNA genes in animals, and current studies show they constitute a minimum of 1% of known genes. We are just beginning to understand the diverse roles they play in cellular processes, which include signaling pathways, developmental pathways, and possibly various types of cancers.

Animals↗