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      miR-526b targets 3′ UTR of MMP1 mRNA

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          Abstract

          Regulation of matrix metalloproteinases (MMPs) is important for many physiological processes involving cancers, inflammation, tissue remodeling and skin aging. Here, we report the novel finding that the expression of MMP1 mRNA is downregulated by the overexpression of miR-526b which is a member of chromosome 19 microRNA cluster (C19MC). Our analysis using reporter constructs containing the 3′ untranslated region (3′ UTR) of MMP1 and its mutant form showed that the region from 377–383 in the 3′ UTR of MMP1 is critical for targeting by miR-526b. In addition, the expression pattern of miR-526b and MMP1 mRNA showed reverse relation between adult dermal and neonatal fibroblasts. We show for the first time that miR-526b, an miRNA belonging to C19MC, can target the 377–383 region of the MMP1 3′ UTR.

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          Most cited references10

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          Gene silencing by microRNAs: contributions of translational repression and mRNA decay.

          Despite their widespread roles as regulators of gene expression, important questions remain about target regulation by microRNAs. Animal microRNAs were originally thought to repress target translation, with little or no influence on mRNA abundance, whereas the reverse was thought to be true in plants. Now, however, it is clear that microRNAs can induce mRNA degradation in animals and, conversely, translational repression in plants. Recent studies have made important advances in elucidating the relative contributions of these two different modes of target regulation by microRNAs. They have also shed light on the specific mechanisms of target silencing, which, although it differs fundamentally between plants and animals, shares some common features between the two kingdoms.
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            RNA polymerase III transcribes human microRNAs.

            Prior work demonstrates that mammalian microRNA (miRNA or miR) expression requires RNA polymerase II (Pol II). However, the transcriptional requirements of many miRNAs remain untested. Our genomic analysis of miRNAs in the human chromosome 19 miRNA cluster (C19MC) revealed that they are interspersed among Alu repeats. Because Alu transcription occurs through RNA Pol III recruitment, and we found that Alu elements upstream of C19MC miRNAs retain sequences important for Pol III activity, we tested the promoter requirements of C19MC miRNAs. Chromatin immunoprecipitation and cell-free transcription assays showed that Pol III, but not Pol II, is associated with miRNA genomic sequence and sufficient for transcription. Moreover, the mature miRNA sequences of approximately 50 additional human miRNAs lie within Alu and other known repetitive elements. These findings extend the current view of miRNA origins and the transcriptional machinery driving their expression.
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              UV-light-induced signal cascades and skin aging.

              L Rittié (2002)
              UV irradiation acts as a broad activator of cell surface growth factor and cytokine receptors. This ligand-independent receptor activation induces multiple downstream signaling pathways that regulate expression of multiple genes. These signaling pathways converge to stimulate transcription factor AP-1. Among genes whose expression is regulated by AP-1 are several matrix-metalloproteinase (MMP) family members and type I procollagen. UV-enhanced matrix degradation is accompanied with decreased collagen production mediated not only by activation of AP-1, but also by inhibition of transforming growth factor (TGF)-beta signaling. Several alterations to skin connective tissue that occur during aging are mediated by mechanisms that are similar to those that occur in response to UV irradiation. Thus, skin aging is associated with increased AP-1 activity, increased MMP expression, impaired TGF-beta signaling, enhanced collagen degradation, and decreased collagen synthesis. Knowledge gained from examining molecular responses of human skin to UV irradiation provides not only a framework for understanding mechanisms involved in skin aging, but also may help in development of new clinical strategies to impede chronological and UV-induced skin aging.
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                Author and article information

                Journal
                Exp Mol Med
                Exp. Mol. Med
                Experimental & Molecular Medicine
                Nature Publishing Group
                1226-3613
                2092-6413
                August 2015
                21 August 2015
                1 August 2015
                : 47
                : 8
                : e178
                Affiliations
                [1 ]Bioscience Research Institute, AmorePacific Corporation R&D Center , Gyeonggi-do, Republic of Korea
                [2 ]Natural Products Research Institute, College of Pharmacy, Seoul National University , Seoul, Republic of Korea
                Author notes
                [* ]Bioscience Research Institute, AmorePacific Corporation R&D Center , Yongin-si, Gyeonggi-do 446–729, Republic of Korea. E-mail: TRLee@ 123456amorepacific.com
                Article
                emm201552
                10.1038/emm.2015.52
                4558487
                26292968
                7f8b5eeb-f0c1-4edd-b737-df2a2ffdfbcb
                Copyright © 2015 KSBMB.

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 26 November 2014
                : 13 April 2015
                : 14 April 2015
                Categories
                Original Article

                Molecular medicine
                Molecular medicine

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