Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation.
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.
Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA.
Lorenzo F
LF
Sempere
Sarah
S
Freemantle
Ian
I
Pitha-Rowe
Eric
E
Moss
Ethan
E
Dmitrovsky
Victor
V
Ambros
D000328:Adult; D000818:Animals; D001921:Brain / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D018236:Carcinoma, Embryonal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D052138:Genes, Neoplasm / Q000502:physiology; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000502:physiology; D012689:Sequence Homology, Nucleic Acid; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology
D029742:Caenorhabditis elegans Proteins; C452195:LIN-28 protein, C elegans; D035683:MicroRNAs; D012333:RNA, Messenger; D012097:Repressor Proteins; D014212:Tretinoin