miRNAs: Whys and Wherefores of miRNA-Mediated Regulation

Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Current Biology (Impact Factor: 9.57). 07/2005; 15(12):R458-60. DOI: 10.1016/j.cub.2005.06.015
Source: PubMed


MiRNAs are assumed to be important in animal development and physiology, but their specific roles in vivo are still poorly understood. New bioinformatic and genetic studies are setting the stage for unraveling the specific biological functions of miRNAs.

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Available from: Eric C Lai, Oct 07, 2015
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    • "MicroRNAs (miRs) are small (18 to 22 nucleotides), non-coding RNAs with post-transcriptional gene silencing activity [6,7] that regulate gene expression by associating with the 3′-untranslated region (3′-UTR) of genes and inhibiting protein translation [8]. miRs can also destabilize and mediate the degradation of RNA transcripts [9]. "
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    ABSTRACT: Background Glioblastoma multiforme (GBM) is the most aggressive type of glioma and carries the poorest chances of survival. There is therefore an urgent need to understand the mechanisms of glioma tumorigenesis and develop or improve therapeutics. The aim of this study was to assess the possible prognostic value of cyclin-dependent kinase 6 (CDK6) and the effects of microRNA-495 (miR-495) manipulation on CDK6 expression and cell survival in glioma cells. Methods Analyses of clinical specimens from GBM patients were used. Expression of CDK6 was analyzed by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry. Expression of CDK6 was also analyzed after over-expression of miR-495 in T98 cells; both cell proliferation and RB phosphorylation were examined. Cell proliferation, cell cycle distribution, and RB phosphorylation were also examined after knockdown of CDK6 in U87-MG and T98 cells. Results Analyses of clinical specimens from GBM patients identified that CDK6 is significantly expressed in gliomas. CDK6 antigen expression was higher in tumor cores and margins than in adjacent normal brain tissues, and higher levels of CDK6 expression in the tumor margin correlated with decreased survival. Over-expression of miR-495 in T98 cells downregulated the expression of CDK6 and inhibited retinoblastoma phosphorylation, and knockdown of CDK6 in U87-MG and T98 cells by siRNAs resulted in cell cycle arrest at the G1/S transition and inhibition of cell proliferation. Conclusions This study revealed miR-495 is down-regulated in glioma tissues. Furthermore, miR-495 regulated CDK6 expression and involved in glioma cell growth inhibition, which indicated the possible role of miR-495 in tumor progression.
    World Journal of Surgical Oncology 04/2013; 11(1):87. DOI:10.1186/1477-7819-11-87 · 1.41 Impact Factor
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    • "The 2–8 nucleotides at the 5′ end of a miRNA are termed the functional ‘seed’ region for the recognition of target mRNAs. The miRNA is loaded into an RNA-induced silencing complex, which decreases translation of the targeted gene product [11,12]. miRNAs have myriad roles in muscle biology and many are expressed in a tissue- and/or stage-specific manner [13]. "
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    ABSTRACT: MicroRNAs (miRNAs) are a type of non-coding small RNA ~22 nucleotides in length that regulate the expression of protein coding genes at the post-transcriptional level. Glycolytic and oxidative myofibers, the two main types of skeletal muscles, play important roles in metabolic health as well as in meat quality and production in the pig industry. Previous expression profile studies of different skeletal muscle types have focused on these aspects of mRNA and proteins; nonetheless, an explanation of the miRNA transcriptome differences between these two distinct muscles types is long overdue. Herein, we present a comprehensive analysis of miRNA expression profiling between the porcine longissimus doris muscle (LDM) and psoas major muscle (PMM) using a deep sequencing approach. We generated a total of 16.62 M (LDM) and 18.46 M (PMM) counts, which produced 15.22 M and 17.52 M mappable sequences, respectively, and identified 114 conserved miRNAs and 89 novel miRNA*s. Of 668 unique miRNAs, 349 (52.25%) were co-expressed, of which 173 showed significant differences (P < 0.01) between the two muscle types. Muscle-specific miR-1-3p showed high expression levels in both libraries (LDM, 32.01%; PMM, 20.15%), and miRNAs that potentially affect metabolic pathways (such as the miR-133 and -23) showed significant differences between the two libraries, indicating that the two skeletal muscle types shared mainly muscle-specific miRNAs but expressed at distinct levels according to their metabolic needs. In addition, an analysis of the Gene Ontology (GO) terms and KEGG pathway associated with the predicted target genes of the differentially expressed miRNAs revealed that the target protein coding genes of highly expressed miRNAs are mainly involved in skeletal muscle structural development, regeneration, cell cycle progression, and the regulation of cell motility. Our study indicates that miRNAs play essential roles in the phenotypic variations observed in different muscle fiber types.
    BMC Molecular Biology 02/2013; 14(1):7. DOI:10.1186/1471-2199-14-7 · 2.19 Impact Factor
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    • "Currently, over 1500 miRNAs have been identified in humans (miRBase 18) [12]. They have a wide variety of expression patterns, and many are differentially expressed during development or disease [13], [14]. More recently, together with components of the inhibitory miRNA-induced silencing complex, they have been identified in postsynaptic densities, indicating that their action maybe restricted, under specific conditions, to discrete loci within cells [15], [16]. "
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    ABSTRACT: Differential RNA localization and local protein synthesis regulate synapse function and plasticity in neurons. MicroRNAs are a conserved class of regulatory RNAs that control mRNA stability and translation in tissues. They are abundant in the brain but the extent into which they are involved in synaptic mRNA regulation is poorly known. Herein, a computational analysis of the coding and 3'UTR regions of 242 presynaptic and 304 postsynaptic proteins revealed that 91% of them are predicted to be microRNA targets. Analysis of the longest 3'UTR isoform of synaptic transcripts showed that presynaptic mRNAs have significantly longer 3'UTR than control and postsynaptic mRNAs. In contrast, the shortest 3'UTR isoform of postsynaptic mRNAs is significantly shorter than control and presynaptic mRNAs, indicating they avert microRNA regulation under specific conditions. Examination of microRNA binding site density of synaptic 3'UTRs revealed that they are twice as dense as the rest of protein-coding transcripts and that approximately 50% of synaptic transcripts are predicted to have more than five different microRNA sites. An interaction map exploring the association of microRNAs and their targets revealed that a small set of ten microRNAs is predicted to regulate 77% and 80% of presynaptic and postsynaptic transcripts, respectively. Intriguingly, many of these microRNAs have yet to be identified outside primate mammals, implicating them in cognition differences observed between high-level primates and non-primate mammals. Importantly, the identified miRNAs have been previously associated with psychotic disorders that are characterized by neural circuitry dysfunction, such as schizophrenia. Finally, molecular dissection of their KEGG pathways showed enrichment for neuronal and synaptic processes. Adding on current knowledge, this investigation revealed the extent of miRNA regulation at the synapse and predicted critical microRNAs that would aid future research on the control of neuronal plasticity and etiology of psychiatric diseases.
    PLoS ONE 10/2012; 7(10):e46189. DOI:10.1371/journal.pone.0046189 · 3.23 Impact Factor
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