Micro-RNAs (miRNAs): genomic organisation, biogenesis and mode of action

Department of Biotechnology, University of Kashmir, Science Block, Hazratbal Campus, Srinagar, Kashmir 190006, India.
Cell and Tissue Research (Impact Factor: 3.33). 05/2012; 349(2):405-13. DOI: 10.1007/s00441-012-1438-0
Source: PubMed

ABSTRACT MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression in animals and in plants. In recent years, miRNAs have been shown to be important biological molecules for regulating various cellular functions. miRNAs function post-transcriptionally usually by base-pairing to the mRNA 3'-untranslated regions of the mRNAs and repress protein synthesis by mechanisms that are not fully understood. Various miRNA genes have been mapped in the genome of a number of organisms and the list continues to grow. Details regarding the genomic organisation, transcriptional regulation and post-transcriptional maturation of miRNAs are still emerging. In this review, information regarding the genomic organisation, biogenesis and regulation of expression of miRNAs is discussed.

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    • "Therefore, the occurrence of 18 R − pre-miRNA entirely by chance is very unlikely. Some authors describe mirtrons as tightly packed between exons [3], but in our analysis we have found that this is not the case. Most mirtrons are surrounded by intronic sequences not exons. "
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    ABSTRACT: Mirtrons are a special type of pre-miRNA which originate from intronic regions and are spliced directly from the transcript instead of being processed by Drosha. The splicing mechanism is better understood for the processing of mRNA for which was established that there is a characteristic CG content around splice sites. Here we analyse the CG-content ratio of pre-miRNAs and mirtrons and compare them with their genomic neighbourhood in an attempt to establish key properties which are easy to evaluate and to understand their biogenesis. We propose a simple log-ratio of the CG-content comparing the precursor sequence and is flanking region. We discovered that Caenorhabditis elegans and Drosophila melanogaster mirtrons, so far without exception, have smaller CG-content than their genomic neighbourhood. This is markedly different from usual pre-miRNAs which mostly have larger CG-content when compared to their genomic neighbourhood. We also analysed some mammalian and primate mirtrons which, in contrast the invertebrate mirtrons, have higher CG-content ratio.
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    ABSTRACT: We aimed to investigate the impact of X-rays on miR-130a and miR-25 expressions of A549 cell lines and to understand the mechanism of miR-130a and miR-25 on the regulation of invasion and metastasis of A549 cell lines. Human adenocarcinoma cells of the line A549 were cultured and radiated by X-rays at the absorbed doses of 2 and 4, respectively by linear accelerator. Transwell invasion and migration assay were employed to exam the metastasis ability of A549 cells post X-rays irradiation. Both the miRNA and mRNA were extracted from A549 cells at different time points post radiation. The expressions of miR-130a and miR-25, as well as the expressions of VEGF and CCR-7 mRNAs, were detected in A549 cells with 2 and 4 Gy X-rays radiation, respectively by real time PCR. Results were statistically analyzed by SAS 8.2 software, which showed that the invasiveness of A549 cells post 2 and 4 Gy X-rays increased significantly compared with that of untreated A549 cells (the migration cell numbers are 20, 48 and 62 in Group 0, 2 and 4 Gy X-rays, respectively). Furthermore, the expressions of miR-130a and miR-25 also increased significantly at the time-points of 1, 2, 4, and 8 h post radiation, and began to decrease to the control level at 12 h post radiation. VEGF and CCR-7 mRNAs were detected to be up-regulated 18 h post radiation and remained at a high level till 72 h post radiation. The expression of VEGF mRNA has a close correlation with that of CCR-7 mRNA, and the expression of miR-130a also has a correlation with that of VEGF and CCR-7mRNAs. It is concluded that the metastasis of A549 cells in vitro could be promoted by X-rays, and miR-130a might play a role in the metastasis of A549 cells via regulating the expressions of VEGF and CCR-7 mRNAs.
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    ABSTRACT: Thrombomodulin (TM) is a 557 amino acid protein with a broad cell and tissue distribution consistent with its wide-ranging physiological roles. When expressed on the lumenal surface of vascular endothelial cells in both large vessels and capillaries, its primary function is to mediate endothelial thromboresistance. The complete integral membrane-bound protein form displays five distinct functional domains, although shorter soluble (functional) variants comprising the extracellular domains have also been reported in fluids such as serum and urine. TM-mediated binding of thrombin is known to enhance the specificity of the latter serine protease towards both protein C and thrombin activatable fibrinolysis inhibitor (TAFI), increasing their proteolytic activation rate by almost three orders of magnitude with concomitant anti-coagulant, anti-fibrinolytic, and anti-inflammatory benefits to the vascular wall. Recent years have seen an abundance of research into the cellular mechanisms governing endothelial TM production, processing, and regulation (including flow-mediated mechanoregulation) - from transcriptional and post-transcriptional (miRNA) regulation of TM gene expression, to post-translational processing and release of the expressed protein - facilitating greater exploitation of its therapeutic potential. The goal of the current paper is to comprehensively review the endothelial/TM system from these regulatory perspectives and draw some fresh conclusions. This paper will conclude with a timely examination of the current status of TMs growing therapeutic appeal - from novel strategies to improve the clinical efficacy of recombinant TM analogs for resolution of vascular disorders such as disseminated intravascular coagulation (DIC), to an examination of the complex pleiotropic relationship between statin treatment and TM expression.
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