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
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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- "miRNAs are processed from primary transcripts with extensive fold-back structures which are transcribed from specific endogenous non protein-coding sequences (MIRNA genes) either from intergenic sequences or in metazoa also within introns. In plants, MIRNA genes are transcribed by RNA polymerase II (Xie et al. 2005a; Megraw et al. 2006) and are expressed in a tissue-and time-specific manner (Lai 2005; Valoczi et al. 2006). Plant miRNAs, function by providing sequence specificity to RISC, which usually slices mRNAs complementary to the miRNAs in a similar way to siRNAs (Llave et al. 2002; Rhoades et al. 2002; Kasschau et al. 2003; Jones-Rhoades et al. 2006), although translational suppression has also been shown (Brodersen et al. 2008). "
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ABSTRACT: Multicellular organisms, like higher plants, need to coordinate their growth and development and to cope with environmental cues. To achieve this, various signal molecules are transported between neighboring cells and distant organs to control the fate of the recipient cells and organs. RNA silencing produces cell non-autonomous signal molecules that can move over short or long distances leading to the sequence specific silencing of a target gene in a well defined area of cells or throughout the entire plant, respectively. The nature of these signal molecules, the route of silencing spread, and the genes involved in their production, movement and reception are discussed in this review. Additionally, a short section on features of silencing spread in animal models is presented at the end of this review. This article is protected by copyright. All rights reserved.
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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 . miRs can also destabilize and mediate the degradation of RNA transcripts . "
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.
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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 . "
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.