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Nonrestrictive developmental regulation of microRNA gene expression

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Abstract

During different periods of mammalian development, global changes in gene expression occur. Developmental changes in global gene expression have been modeled as a restrictive process. To test the restriction model of global changes in gene expression, we have used embryonic stem (ES) cells as a model system for the early mammalian embryo. ES cells are pluripotent cells that can contribute to all cellular lineages of the developing mammalian fetus and are derived from early embryonic cells. Using this model system, we have studied a new class of RNAs called microRNAs that have been identified and shown to play a role in the direct regulation of messenger RNAs. Here we report the expression signature for 248 microRNAs in 13 independent murine ES cells, embryoid bodies, and somatic tissues. The expression profile for 248 mouse microRNAs was determined for embryonic stem cells, embryoid bodies, mouse embryos, mature heart, lung, liver, kidney, and brain. Characteristic microRNA expression signatures were observed for each evaluated sample. When the characteristic microRNA signatures for developmentally ordered samples were compared, immature samples exhibited a less complex microRNA transcript profile than did mature samples. Our data support a progressive model of microRNA gene expression. Based on the progressive increase in complexity of micro- RNA expression, we hypothesize that the mammalian developmental program requires a temporal coupling of expression between microRNAs and messenger RNAs to enable the developmental potential observed in mammalian ontogeny.

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References

  • Armstrong L, Lako M, Lincoln J, Cairns PM, Hole N, et al. (2000) mTert expression correlates with telomerase activity during the differentiation of murine embryonic stem cells. Mech Dev 97(1–2), 109–116

    Article  PubMed  CAS  Google Scholar 

  • Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, et al. (2003) Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev 17(1), 126–140

    Article  PubMed  CAS  Google Scholar 

  • Cai X, Hagedorn CH, Cullen BR (2004) Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10(12), 1957–1966

    Article  PubMed  CAS  Google Scholar 

  • Chambers I, Colby D, Robertson M, Nichols J, Lee S, et al. (2003) Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113(5), 643–655

    Article  PubMed  CAS  Google Scholar 

  • Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, et al. (2005) Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 33(20), e179

    Article  PubMed  CAS  Google Scholar 

  • Davidson E (1986) Gene Activity in Early Development (New York: Academic Press)

    Google Scholar 

  • Doetschman TC, Eistetter H, Katz M, Schmitt W, Kemler R, et al. (1985) The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J Embryol Exp Morphol 87, 27–45

    PubMed  CAS  Google Scholar 

  • Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. PNAS USA 95(25), 14863–14868

    Article  PubMed  CAS  Google Scholar 

  • Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292(5819), 154–156

    Article  PubMed  CAS  Google Scholar 

  • Galau GA, Klein WH, Davis MM, Wold BJ, Britten RJ, et al. (1976) Structural gene sets active in embryos and adult tissues of the sea urchin. Cell 7(4), 487–505

    Article  PubMed  CAS  Google Scholar 

  • Geijsen N, Horoschak M, Kim K, Gribnau J, Eggan K, et al. (2004) Derivation of embryonic germ cells and male gametes from embryonic stem cells. Nature 427(6970), 148–154

    Article  PubMed  CAS  Google Scholar 

  • Griffiths-Jones S (2004) The microRNA registry. Nucleic Acids Res 32(Database issue), D109–D111

    CAS  Google Scholar 

  • Houbaviy HB, Murray MF, Sharp PA (2003) Embryonic stem cell-specific MicroRNAs. Dev Cell 5(2), 351–358

    Article  PubMed  CAS  Google Scholar 

  • Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, et al. (2001) A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293(5531), 834–838

    Article  PubMed  CAS  Google Scholar 

  • Ketting RF, Fischer SE, Bernstein E, Sijen T, Hannon GJ, et al. (2001) Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15(20), 2654–2659

    Article  PubMed  CAS  Google Scholar 

  • Lee R, Feinbaum R, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes a small RNAs with antisense complementarity to lin-14. Cell 75(5), 843–854

    Article  PubMed  CAS  Google Scholar 

  • Lee Y, Ahn C, Han J, Choi H, Kim J, et al. (2003) The nuclear RNase II Drosha initiates microRNA processing. Nature 425, 415–419

    Article  PubMed  CAS  Google Scholar 

  • Lee Y, Kim M, Han J, Yeom KH, Lee S, et al. (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23(20), 4051–4060

    Article  PubMed  CAS  Google Scholar 

  • Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78(12), 7634–7638

    Article  PubMed  CAS  Google Scholar 

  • Nagy A, Gertsenstein M, Vintersten K, Behringer R, et al. (2004) Manipulating the Mouse Embryo: A Laboratory Manual (Cold Spring Harbor, NY: Cold Spring Harbor Press)

    Google Scholar 

  • Olsen PH, Ambros V (1999) The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol 216(2), 671–680

    Article  PubMed  CAS  Google Scholar 

  • Palmieri SL, Peter W, Hess H, Scholer HR (1994) Oct-4 transcription factor is differentially expressed in the mouse embryo during establishment of the first two extraembryonic cell lineages involved in implantation. Dev Biol 166(1), 259–267

    Article  PubMed  CAS  Google Scholar 

  • Parizotto EA, Dunoyer P, Rahm N, Himber C, Voinnet O (2004) In vivo investigation of the transcription, processing, endonucleolytic activity, and functional relevance of the spatial distribution of a plant miRNA. Genes Dev 18(18), 2237–2242

    Article  PubMed  CAS  Google Scholar 

  • Pasquinelli AE, Ruvkun G (2002) Control of developmental timing by microRNAs and their targets. Annu Rev Cell Dev Biol 18, 495–513

    Article  PubMed  CAS  Google Scholar 

  • Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA (2002) “Stemness”: transcriptional profiling of embryonic and adult stem cells. Science 298(5593), 597–600

    Article  PubMed  CAS  Google Scholar 

  • Rogers MB, Hosler BA, Gudas LJ (1991) Specific expression of a retinoic acid-regulated, zinc-finger gene, Rex-1, in preimplantation embryos, trophoblast and spermatocytes. Development 113(3), 815–824

    PubMed  CAS  Google Scholar 

  • Southgate TD, Bain D, Fairbanks LD, Morelli AE, Larregina AT, et al. (1999) Adenoviruses encoding HPRT correct biochemical abnormalities of HPRT-deficient cells and allow their survival in negative selection medium. Metab Brain Dis 14(4), 205–221

    Article  PubMed  CAS  Google Scholar 

  • Suh MR, Lee Y, Kim JY, Kim SK, Moon SH, et al. (2004) Human embryonic stem cells express a unique set of microRNAs. Dev Biol 270(2), 488–498

    Article  PubMed  CAS  Google Scholar 

  • Thompson S, Clarke AR, Pow AM, Hooper ML, Melton DW (1989) Germ line transmission and expression of a corrected HPRT gene produced by gene targeting in embryonic stem cells. Cell 56(January), 313–321

    Google Scholar 

  • Toyooka Y, Tsunekawa N, Takahashi Y, Matsui Y, Satoh M, et al. (2000) Expression and intracellular localization of mouse Vasa-homologue protein during germ cell development. Mech Dev 93(1–2), 139–149

    Article  PubMed  CAS  Google Scholar 

  • Wightman B, Ha I, Ruvkun G (1993) Posttanscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75(5), 855–862

    Article  PubMed  CAS  Google Scholar 

  • Ying QL, Smith AG (2003) Defined conditions for neural commitment and differentiation. Methods Enzymol 365, 327–341

    Article  PubMed  CAS  Google Scholar 

  • Zijlstra M, Li E, Sajjadi F, Subramani S, Jaenisch R (1989) Germ line transmission of a disrupted (2-microglobulin gene produced by homologous recombination in embryonic stem cells. Nature 342, 435–438

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank Kristina Sower for technical assistance. This research was supported by the W. M. Keck Foundation initiative in RNA science at the University of Colorado and by NIHGMS: GM61079 awarded to WMS.

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Correspondence to William M. Strauss.

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Strauss, W.M., Chen, C., Lee, CT. et al. Nonrestrictive developmental regulation of microRNA gene expression. Mamm Genome 17, 833–840 (2006). https://doi.org/10.1007/s00335-006-0025-7

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  • DOI: https://doi.org/10.1007/s00335-006-0025-7

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