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

By L. Sempere, S. Freemantle, I. Pitha-Rowe, E. Moss, E. Dmitrovsky, V. Ambros. Genome Biology, 2004

1,640 citations recorded by the source corpus.

BackgroundThe 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.ResultsIn 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.ConclusionsThe 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a1668d8c3f9ba699860e1e0ab6531e1de3bb3bb9

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Citations in the corpus

Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAs. (2007, background): “As observed previously in worms and mammals (Lau et al. 2001; Sempere et al. 2004; Baskerville and Bartel 2005), miRNAs that were clustered in the Drosophila genome usually had similar expression profiles (Fig.”
MicroRNAs accurately identify cancer tissue origin (2008, positive): “This framework is set up to utilize the potential specificity of miRNAs in tissue differentiation and embryogenesis: different miRNAs may be involved in various stages of tissue specificatio”
The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. (2007, background): “Although a number of miRNAs are expressed in the NS (Kim et al., 2004; Krichevsky et al., 2003; Miska et al., 2004; Sempere et al., 2004), relatively little is known about their functions (Ashraf et al.”
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Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. (2005, background): “The coexpression of closely clustered miRNAs has been used as evidence that they derive from a common primary transcript (Lau et al. 2001; Sempere et al. 2004), and for a few human and fly miRNA clusters, RT-PCR has confirmed the presence of a polycistronic transcript (Lee et al. 2002, 2004; Aravin…”
Prediction and validation of microRNAs and their targets (2005, positive): “Northern blots are successfully used to validate predicted microRNAs [25], and still are considered a golden standard.”