MicroRNA-184 downregulates nuclear receptor corepressor 2 in mouse spermatogenesis

BackgroundThere have been increasing attentions on the role of small RNAs, especially microRNAs in post-transcriptional gene regulation during spermatogenesis. MicroRNA-184 (miR-184) has been shown to be mainly expressed in the testis and brain, and that its expression levels are by far the highest in the testis. However, the role of miR-184 in mammalian spermatogenesis remains unclear.ResultsIn this study, we demonstrated that miR-184 levels were increased during mouse postnatal testis development. Specifically, miR-184 expression was restricted to the germ cells from spermatogonia to round spermatids. Overexpression of miR-184 promoted the proliferation of a germ cell line, GC-1spg. Moreover, miR-184 downregulated nuclear receptor corepressor 2 (Ncor2) by targeting its 3' untranslated region through inhibiting NCOR2 protein translation.ConclusionsMiR-184 may be involved in the post-transcription regulation of mRNAs such as Ncor2 in mammalian spermatogenesis.

[1]  Eugene Berezikov,et al.  Detection of microRNAs in frozen tissue sections by fluorescence in situ hybridization using locked nucleic acid probes and tyramide signal amplification , 2007, Nature Protocols.

[2]  William Ignace Wei,et al.  Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue , 2008, Clinical Cancer Research.

[3]  T. Tuschl,et al.  New microRNAs from mouse and human. , 2003, RNA.

[4]  Izuho Hatada,et al.  MeCP2-dependent repression of an imprinted miR-184 released by depolarization. , 2008, Human molecular genetics.

[5]  Yongxin Ma,et al.  A microarray for microRNA profiling in mouse testis tissues. , 2007, Reproduction.

[6]  Mariette Schrier,et al.  A Genetic Screen Implicates miRNA-372 and miRNA-373 As Oncogenes in Testicular Germ Cell Tumors , 2006, Cell.

[7]  T. Hennet,et al.  Differential regulation of the zebrafish orthopedia1 gene during fate determination of diencephalic neurons , 2006, BMC Developmental Biology.

[8]  Wei Yan,et al.  Cloning and expression profiling of testis-expressed microRNAs. , 2007, Developmental biology.

[9]  S. Short,et al.  SMRT has tissue-specific isoform profiles that include a form containing one CoRNR box. , 2005, Biochemical and biophysical research communications.

[10]  Jidong Liu,et al.  Control of protein synthesis and mRNA degradation by microRNAs. , 2008, Current opinion in cell biology.

[11]  N. Spinner,et al.  Unique forms of human and mouse nuclear receptor corepressor SMRT. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  E. M. Eddy Regulation of gene expression during spermatogenesis. , 1998, Seminars in cell & developmental biology.

[13]  H. Tian,et al.  Downregulation of microRNA-383 is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation by targeting IRF1 , 2010, Cell Death and Disease.

[14]  A. Mantovani,et al.  B-myb antisense oligonucleotides inhibit proliferation of human hematopoietic cell lines. , 1992, Blood.

[15]  R. Evans,et al.  A transcriptional co-repressor that interacts with nuclear hormone receptors , 1995, Nature.

[16]  R. Lavker,et al.  MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity. , 2006, Molecular vision.

[17]  M. Fiscella,et al.  Constitutive expression of B-myb can bypass p53-induced Waf1/Cip1-mediated G1 arrest. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[18]  J. Millán,et al.  Immortalized germ cells undergo meiosis in vitro. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Ligang Wu,et al.  Let me count the ways: mechanisms of gene regulation by miRNAs and siRNAs. , 2008, Molecular cell.

[20]  M. Goodson,et al.  Alternative mRNA Splicing of SMRT Creates Functional Diversity by Generating Corepressor Isoforms with Different Affinities for Different Nuclear Receptors* , 2005, Journal of Biological Chemistry.

[21]  F. Zindy,et al.  Control of Spermatogenesis in Mice by the Cyclin D-Dependent Kinase Inhibitors p18Ink4c and p19Ink4d , 2001, Molecular and Cellular Biology.

[22]  R. Braun,et al.  Post-transcriptional control of gene expression during spermatogenesis. , 1998, Seminars in cell & developmental biology.

[23]  C. Glass,et al.  The coregulator exchange in transcriptional functions of nuclear receptors. , 2000, Genes & development.

[24]  U. Gaul,et al.  miR-184 has multiple roles in Drosophila female germline development. , 2009, Developmental cell.

[25]  Zuoren Yu,et al.  MicroRNA Mirn122a Reduces Expression of the Posttranscriptionally Regulated Germ Cell Transition Protein 2 (Tnp2) Messenger RNA (mRNA) by mRNA Cleavage1 , 2005, Biology of reproduction.

[26]  Kai Stühler,et al.  Identification and Functional Characterization of microRNAs Involved in the Malignant Progression of Gliomas , 2010, Brain pathology.

[27]  H. Horvitz,et al.  MicroRNA Expression in Zebrafish Embryonic Development , 2005, Science.

[28]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[29]  M. O'sullivan,et al.  MicroRNA-184 inhibits neuroblastoma cell survival through targeting the serine/threonine kinase AKT2 , 2010, Molecular Cancer.

[30]  C. Burge,et al.  Prediction of Mammalian MicroRNA Targets , 2003, Cell.

[31]  D. McDonnell,et al.  The Transcription Factor B-Myb Is Maintained in an Inhibited State in Target Cells through Its Interaction with the Nuclear Corepressors N-CoR and SMRT , 2002, Molecular and Cellular Biology.

[32]  R. Stallings,et al.  Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis. , 2007, Cancer research.

[33]  M. Azim Surani,et al.  MicroRNA Biogenesis Is Required for Mouse Primordial Germ Cell Development and Spermatogenesis , 2008, PloS one.

[34]  Á. Pascual,et al.  Nuclear hormone receptors and gene expression. , 2001, Physiological reviews.