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At least 253 records · Page 14Linked to original sources

PubMed2005

The temporal patterning microRNA let-7 regulates several transcription factors at the larval to adult transition in C. elegans.

The let-7 microRNA is phylogenetically conserved and temporally expressed in many animals. C. elegans let-7 controls terminal differentiation in a stem cell-like lineage in the hypodermis, while human let-7 has been implicated in lung cancer. To elucidate let-7's role in temporal control of nematode development, we used sequence analysis and reverse genetics to identify candidate let-7 target genes. We show that the nuclear hormone receptor daf-12 is a let-7 target in seam cells, while the forkhead transcription factor pha-4 is a target in the intestine. Additional likely targets are the zinc finger protein die-1 and the putative chromatin remodeling factor lss-4. Together with the previous identification of the hunchback ortholog hbl-1 as a let-7 target in the ventral nerve cord, our findings show that let-7 acts in at least three tissues to regulate different transcription factors, raising the possibility of let-7 as a master temporal regulator.

Animals↗

PubMed2005

Specific effects of microRNAs on the plant transcriptome.

Most plant microRNAs (miRNAs) have perfect or near-perfect complementarity with their targets. This is consistent with their primary mode of action being cleavage of target mRNAs, similar to that induced by perfectly complementary small interfering RNAs (siRNAs). However, there are natural targets with up to five mismatches. Furthermore, artificial siRNAs can have substantial effects on so-called off-targets, to which they have only limited complementarity. By analyzing the transcriptome of plants overexpressing different miRNAs, we have deduced a set of empirical parameters for target recognition. Compared to artificial siRNAs, authentic plant miRNAs appear to have much higher specificity, which may reflect their coevolution with the remainder of the transcriptome. We also demonstrate that miR172, previously thought to act primarily by translational repression, can efficiently guide mRNA cleavage, although the effects on steady-state levels of target transcripts are obscured by strong feedback regulation. This finding unifies the view of plant miRNA action.

Base Pairing↗

PubMed2006

The diverse functions of microRNAs in animal development and disease.

MicroRNAs (miRNAs) control gene expression by translational inhibition and destabilization of mRNAs. While hundreds of miRNAs have been found, only a few have been studied in detail. miRNAs have been implicated in tissue morphogenesis, cellular processes like apoptosis, and major signaling pathways. Emerging evidence suggests a direct link between miRNAs and disease, and miRNA expression signatures are associated with various types of cancer. In addition, the gain and loss of miRNA target sites appears to be causal to some genetic disorders. Here, we discuss the current literature on the role of miRNAs in animal development and disease.

Animal Diseases↗

PubMed2005

Stage-specific expression of microRNAs during Xenopus development.

MicroRNAs (miRNAs) repress target genes at the post-transcriptional level and play important roles in development and cell lineage decision. However, in vertebrates, both the targets of miRNAs and their expression profile during development are poorly understood. Here, we report the detailed expression profiles of miRNAs from oocyte stage to tadpole stage in Xenopus laevis. As development proceeds, a variety of miRNAs start to be expressed. Most miRNAs emerged at a specific stage and were continuously expressed until the tadpole stage. In addition, we identified a novel miRNA that was expressed only at specific stages of development and that is likely to have roles in midblastula transition.

Animals↗

PubMed2005

MicroRNA function in animal development.

MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate gene expression by base-pairing to mRNAs. Hundreds of miRNAs have been identified in various multicellular organisms and many miRNAs are evolutionarily conserved. Although the biological functions of most miRNAs are unknown, miRNAs are predicted to regulate up to 30% of the genes within the human genome. Gradually, we are beginning to understand the functions of individual miRNAs and the general function of miRNA action. Here, we review the recent advances in miRNA biology in animals. Particularly, we focus on the roles of miRNAs in vertebrate development and disease.

Animals↗

PubMed2005

MicroRNA biogenesis and function in plants.

A microRNA (miRNA) is a 21-24 nucleotide RNA product of a non-protein-coding gene. Plants, like animals, have a large number of miRNA-encoding genes in their genomes. The biogenesis of miRNAs in Arabidopsis is similar to that in animals in that miRNAs are processed from primary precursors by at least two steps mediated by RNAse III-like enzymes and that the miRNAs are incorporated into a protein complex named RISC. However, the biogenesis of plant miRNAs consists of an additional step, i.e., the miRNAs are methylated on the ribose of the last nucleotide by the miRNA methyltransferase HEN1. The high degree of sequence complementarity between plant miRNAs and their target mRNAs has facilitated the bioinformatic prediction of miRNA targets, many of which have been subsequently validated. Plant miRNAs have been predicted or confirmed to regulate a variety of processes, such as development, metabolism, and stress responses. A large category of miRNA targets consists of genes encoding transcription factors that play important roles in patterning the plant form.

Animals↗

PubMed2006

Identification of new central nervous system specific mouse microRNAs.

MicroRNAs (miRNAs) are small regulatory molecules suppressing mRNA activity in metazoans. Here we describe two new miRNAs cloned from brain tissue of mouse embryos. These miRNAs are expressed mainly during embryogenesis and specifically in the central nervous system. We also established the expression patterns of three recently identified miRNAs that were found in our short RNA library. All of them were expressed in the brain and spinal chord but while miR-410 and miR-431 were central nervous system specific, miR-500 was also expressed in limb buds. In addition, the expression of miR-500 in limb buds showed very strong asymmetry in favour of the left hand side.

Animals↗

PubMed2006

Transgenically expressed viral RNA silencing suppressors interfere with microRNA methylation in Arabidopsis.

HEN1-dependent methylation of the 3'-terminal nucleotide is a crucial step in plant microRNA (miRNA) biogenesis. Here we report that several viral RNA silencing suppressors (P1/HC-Pro, p21 and p19) inhibit miRNA methylation. These suppressors have distinct effects on different miRNAs. We also show that miRNA* is methylated in vivo in a suppressor-sensitive manner, suggesting that the viral proteins interfere with miRNA/miRNA* duplexes. p19 and p21 bind both methylated and unmethylated miRNA/miRNA* duplexes in vivo. These findings suggest miRNA/miRNA* as the in vivo substrates for the HEN1 miRNA methyltransferase and raise intriguing possibilities regarding the cellular location of miRNA methylation.

Arabidopsis↗

PubMed2006

Identification of 188 conserved maize microRNAs and their targets.

MicroRNAs (miRNAs) represent a newly identified class of non-protein-coding approximately 20nt small RNAs which play important roles in multiple biological processes by degrading targeted mRNAs or repressing mRNA translation. After searching a genomic survey sequence database using homologs and secondary structures, we found 188 maize miRNAs belonging to 29 miRNA families. Of the 188 maize miRNA genes, 28 (15%) were found in at least one EST. A total of 115 potential targets were identified for 26 of the miRNA families based on the fact that miRNAs exhibit perfect or nearly perfect complementarity with their target sequences. A majority of the targets are transcription factors which play important roles in maize development, including leaf, shoot, and root development. Additionally, these maize miRNAs are also involved in other cellular processes, such as signal transduction, stress response, sucrose and cellulose synthesis, and ubiquitin protein degradation pathway. Some of the newly identified miRNA targets may be unique to maize.

Base Sequence↗

PubMed2006

The cartilage specific microRNA-140 targets histone deacetylase 4 in mouse cells.

MicroRNAs (miRNA) are short RNA molecules regulating the expression of specific mRNAs. We investigated the expression pattern and potential targets of mouse miR-140 and found that miR-140 is specifically expressed in cartilage tissues of mouse embryos during both long and flat bone development. MiR-140 expression was detected in the limbs of E11.5 embryos in the primorida of future bones both in the fore and hindlimb and across autopod, zeugopod and stylopod. All digits of E14.5 fore- and hindlimbs showed accumulation of miR-140, except the first digit of the hindlimb. MiR-140 expression was also detected in the cartilagenous base of E17.5 skulls and in the sternum, the proximal rib heads and the developing vertebral column of E15.5 embryos. A potential target of miR-140, histone deacetylase 4, was validated experimentally and the possible role of miR-140 in long bone development is discussed.

Animals↗

PubMed2005

MicroRNAs as oncogenes.

MicroRNAs (miRNAs) are a class of non-coding RNAs that function as endogenous triggers of the RNA interference pathway. Originally discovered in Caenorhabditis elegans, this group of tiny RNAs has moved to the forefront of biology. With over 300 miRNA genes identified in the human genome, and a plethora of predicted mRNA targets, it is believed that these small RNAs have a central role in diverse cellular and developmental processes. Concordant with this, aberrant expression of miRNA genes could lead to human disease, including cancer. Although the connection of miRNAs with cancer has been suspected for several years, four recent studies have confirmed the suspicion that miRNAs regulate cell proliferation and apoptosis, and play a role in cancer.

Animals↗

PubMed2004

Intron-derived microRNAs--fine tuning of gene functions.

New evidence suggests that abundant small RNAs, microRNAs (miRNAs) act as regulatory vehicles to repress translation or cleave RNA transcripts, depending on their complementarity to the target gene, and result in modulation of gene expression. This review describes that the miRNAs derived from introns can suppress intracellular RNA homologues and regulate the gene function.

Animals↗

PubMed2005

Computational analysis of microRNA targets in Caenorhabditis elegans.

MicroRNAs (miRNAs) are endogenous approximately 22-nucleotide (nt) non-coding RNAs that post-transcriptionally regulate the expression of target genes via hybridization to target mRNA. Using known pairs of miRNA and target mRNA in Caenorhabditis elegans, we first performed computational analysis for specific hybridization patterns between these two RNAs. We counted the numbers of perfectly complementary dinucleotide sequences and calculated the free energy within complementary base pairs of each dinucleotide, observed by sliding a 2-nt window along all nucleotides of the miRNA-mRNA duplex. We confirmed not only strong base pairing within the 5' region of miRNAs (nts 1-8) in C. elegans, but also the required mismatch within the central region (nt 9 or nt 10), and we found weak binding within the 3' region (nts 13-14). We also predicted 687 possible miRNA target transcripts, many of which are thought to be involved in C. elegans development, by combining the above mentioned hybridization tendency with the following analyses: (1) prediction of the miRNA-mRNA duplex with free-energy minimization; (2) identification of the complementary pattern within the miRNA-mRNA duplex; (3) conservation of target sites between C. elegans and C. briggsae, a related soil nematode; and (4) extraction of mRNA candidates with multiple target sites. Rigorous tests using shuffled miRNA controls supported these predictions. Our results suggest that miRNAs recognize their target mRNAs by their hybridization pattern and that many target mRNAs may be regulated through a combination of several specific miRNA target sites in C. elegans.

3' Untranslated Regions↗

PubMed2006

Expression profile analysis of microRNA (miRNA) in mouse central nervous system using a new miRNA detection system that examines hybridization signals at every step of washing.

MicroRNAs (miRNAs) are small noncoding RNAs, with a length of 19 to 23 nucleotides, which appear to be involved in the regulation of gene expression by inhibiting the translation of messenger RNA. Expression profile analysis of miRNAs is necessary to understand their complex role in the regulation of gene expression during the development and differentiation of cells and in various tissues. We describe here a detection system for miRNA expression profiles, using a new type of DNA chip and fluorescent labeled cellular RNAs, which allows real-time detection of hybridization signals at every step of washing and results in highly reproducible miRNA expression profiles. Using the system, we investigated the expression profiles of miRNA in the mouse central nervous system (CNS), namely the spinal cord, medulla oblongata, pons, cerebellum, midbrain, diencephalons, and cerebral hemispheres. The results indicated that although the CNS subregions expressed similar miRNA genes, the expression levels of the miRNAs varied among the subregions, suggesting that the CNS subregions specialized for different functions possess different expression profiles of miRNAs.

Animals↗

PubMed2026

MicroRNA-driven regulatory networks in aphid ecological adaptation: integrating stress tolerance, dispersal plasticity, and population expansion.

Aphids (Hemiptera: Aphididae) are important agricultural pests and exhibit strong ecological adaptability, allowing them to persist under stress, disperse to new habitats, and rapidly increase population size. Recent advances in functional genomics have identified microRNAs (miRNAs) as key post-transcriptional regulators involved in these processes, yet their roles have remained fragmented across studies. Here, we synthesize current evidence into a "three-stage framework", encompassing population maintenance under stress, dispersal to new habitats, and population expansion upon establishment. We highlight how miRNAs regulate detoxification pathways (e.g., P450s, UGTs, ABC transporters), mediate interactions with host plants and symbionts, and integrate hormonal signaling networks including insulin, juvenile hormone, and ecdysteroid pathways. This framework identifies candidate miRNAs, target genes, and signaling pathways that may recur across different ecological contexts, including stress responses, dispersal-related plasticity, and reproductive regulation. However, direct evidence demonstrating that candidate shared miRNA regulators coordinate multiple life-history stages remains limited and requires further experimental validation. We critically evaluate the strength of functional evidence, distinguishing experimentally validated miRNA-target interactions from prediction- or expression-based associations. Finally, we discuss emerging applications of miRNA-based pest control, including artificial miRNAs, RNAi technologies, and nanocarrier delivery systems. By linking molecular mechanisms with ecological outcomes, this review provides a synthesis and highlights miRNAs as important regulators of aphid adaptation and candidate targets for sustainable management strategies.

Aphids↗

PubMed2006

Detection of the argonaute protein Ago2 and microRNAs in the RNA induced silencing complex (RISC) using a monoclonal antibody.

MicroRNAs (miRNAs) are short RNA molecules responsible for post-transcriptional gene silencing by the degradation or translational inhibition of their target messenger RNAs (mRNAs). This process of gene silencing, known as RNA interference (RNAi), is mediated by highly conserved Argonaute (Ago) proteins which are the key components of the RNA induced silencing complex (RISC). In humans, Ago2 is responsible for the endonuclease cleavage of targeted mRNA and it interacts with the mRNA-binding protein GW182, which is a marker for cytoplasmic foci referred to as GW bodies (GWBs). We demonstrated that the anti-Ago2 monoclonal antibody 4F9 recognized GWBs in a cell cycle dependent manner and was capable of capturing miRNAs associated with Ago2. Since Ago2 protein is the effector protein of RNAi, anti-Ago2 monoclonal antibody may be useful in capturing functional miRNAs.

Animals↗

PubMed2006

A novel method to detect functional microRNA targets.

MicroRNA (miRNA) molecules are non-coding RNAs, 19 to 24 nt in length that have been identified recently as important regulators of gene expression. Several computational methods have been developed to describe the target recognition mechanism by miRNA. We propose here a novel method to detect miRNA-mRNA complexes in eukaryotic cells. As a first step, we synthesize cDNA on an mRNA template using miRNAs as the endogenous cytoplasmic primer. This step extends miRNA and overcomes the problem of low complementary binding of miRNAs to their targets. Purified hybrid 3'-cDNA-miRNA-5' molecules are used in a second round of reverse transcription to anneal to target mRNA in a highly gene-specific manner. The 5'-end analysis of these cDNA molecules demonstrated that primers for cDNAs were "signatures" of miRNA molecules, and over-expression of their full-length mature miRNAs resulted in functional inhibition of target protein expression.

Base Sequence↗

PubMed2005

HIV may produce inhibitory microRNAs (miRNAs) that block production of CD28, CD4 and some interleukins.

It is well-known that HIV-1 infection results in a gradual decline of the CD4+ T-lymphocytes, but the underlying mechanism of this decline is not completely understood. Research has shown that HIV-1 infection of CD4+ T cells results in decreased CD28 expression, but the mechanism of this repression is unknown. There is also substantial evidence demonstrating regulatory involvement of microRNA (miRNA) during protein expression in plants and some animals, and reports have recently been published confirming the existence of viral-encoded miRNAs. Based on these findings, we hypothesize that viral-encoded miRNA from HIV-1 may directly alter T cell, macrophage and dendritic cell activity. To investigate a potential correlation between the genomic complementarity of HIV-1 and host cell protein expression, a local alignment search was performed to assess for regions of complementarity between the HIV-1 proviral genome and the mRNA coding sequence of various proteins expressed by CD+ T cells and macrophages. Regions of complementarity with strong correlations to the currently established criteria for miRNA:target mRNA activity were found between HIV-1 and CD28, CTLA-4 and some interleukins, suggesting that HIV-1 may produce translational repression in host cells.

Base Sequence↗