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      Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation

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          Abstract

          Northern blot analysis of 119 previously reported microRNAs in adult organs from mouse and human identified a subset of brain-expressed miRNAs whose expression behavior is conserved in both mouse and human differentiating neurons, implicating these microRNAs in mammalian neuronal development or function

          Abstract

          Background

          The microRNAs (miRNAs) are an extensive class of small noncoding RNAs (18 to 25 nucleotides) with probable roles in the regulation of gene expression. In Caenorhabditis elegans, lin-4 and let-7 miRNAs control the timing of fate specification of neuronal and hypodermal cells during larval development. lin-4, let-7 and other miRNA genes are conserved in mammals, and their potential functions in mammalian development are under active study.

          Results

          In order to identify mammalian miRNAs that might function in development, we characterized the expression of 119 previously reported miRNAs in adult organs from mouse and human using northern blot analysis. Of these, 30 miRNAs were specifically expressed or greatly enriched in a particular organ (brain, lung, liver or skeletal muscle). This suggests organ- or tissue-specific functions for miRNAs. To test if any of the 66 brain-expressed miRNAs were present in neurons, embryonal carcinoma cells were treated with all- trans-retinoic acid to promote neuronal differentiation. A total of 19 brain-expressed miRNAs (including lin-4 and let-7 orthologs) were coordinately upregulated in both human and mouse embryonal carcinoma cells during neuronal differentiation. The mammalian ortholog of C. elegans lin- 28, which is downregulated by lin-4 in worms via 3' untranslated region binding, was also repressed during neuronal differentiation of mammalian embryonal carcinoma cells. Mammalian lin-28 messenger RNAs contain conserved predicted binding sites in their 3' untranslated regions for neuron-expressed miR-125b (a lin-4 ortholog), let-7a, and miR-218.

          Conclusions

          The identification of a subset of brain-expressed miRNAs whose expression behavior is conserved in both mouse and human differentiating neurons implicates these miRNAs in mammalian neuronal development or function.

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          Most cited references33

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          An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.

          Two small temporal RNAs (stRNAs), lin-4 and let-7, control developmental timing in Caenorhabditis elegans. We find that these two regulatory RNAs are members of a large class of 21- to 24-nucleotide noncoding RNAs, called microRNAs (miRNAs). We report on 55 previously unknown miRNAs in C. elegans. The miRNAs have diverse expression patterns during development: a let-7 paralog is temporally coexpressed with let-7; miRNAs encoded in a single genomic cluster are coexpressed during embryogenesis; and still other miRNAs are expressed constitutively throughout development. Potential orthologs of several of these miRNA genes were identified in Drosophila and human genomes. The abundance of these tiny RNAs, their expression patterns, and their evolutionary conservation imply that, as a class, miRNAs have broad regulatory functions in animals.
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            The microRNAs of Caenorhabditis elegans.

            MicroRNAs (miRNAs) are an abundant class of tiny RNAs thought to regulate the expression of protein-coding genes in plants and animals. In the present study, we describe a computational procedure to identify miRNA genes conserved in more than one genome. Applying this program, known as MiRscan, together with molecular identification and validation methods, we have identified most of the miRNA genes in the nematode Caenorhabditis elegans. The total number of validated miRNA genes stands at 88, with no more than 35 genes remaining to be detected or validated. These 88 miRNA genes represent 48 gene families; 46 of these families (comprising 86 of the 88 genes) are conserved in Caenorhabditis briggsae, and 22 families are conserved in humans. More than a third of the worm miRNAs, including newly identified members of the lin-4 and let-7 gene families, are differentially expressed during larval development, suggesting a role for these miRNAs in mediating larval developmental transitions. Most are present at very high steady-state levels-more than 1000 molecules per cell, with some exceeding 50,000 molecules per cell. Our census of the worm miRNAs and their expression patterns helps define this class of noncoding RNAs, lays the groundwork for functional studies, and provides the tools for more comprehensive analyses of miRNA genes in other species.
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              • Record: found
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              • Article: not found

              Vertebrate microRNA genes.

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                Author and article information

                Journal
                Genome Biol
                Genome Biology
                BioMed Central (London )
                1465-6906
                1465-6914
                2004
                16 February 2004
                : 5
                : 3
                : R13
                Affiliations
                [1 ]Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA
                [2 ]Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA
                [3 ]Department of Molecular Biology, University of Medicine and Dentistry of NJ, Stratford, NJ 08084, USA
                [4 ]Department of Medicine and Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA
                Article
                gb-2004-5-3-r13
                10.1186/gb-2004-5-3-r13
                395763
                15003116
                40b90761-0ea2-40c2-83a3-80648149f01f
                Copyright © 2004 Sempere et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
                History
                : 17 October 2003
                : 18 November 2003
                : 8 January 2004
                Categories
                Research

                Genetics
                Genetics

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