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Ancient animal microRNAs and the evolution of tissue identity

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Abstract

The spectacular escalation in complexity in early bilaterian evolution correlates with a strong increase in the number of microRNAs1,2. To explore the link between the birth of ancient microRNAs and body plan evolution, we set out to determine the ancient sites of activity of conserved bilaterian microRNA families in a comparative approach. We reason that any specific localization shared between protostomes and deuterostomes (the two major superphyla of bilaterian animals) should probably reflect an ancient specificity of that microRNA in their last common ancestor. Here, we investigate the expression of conserved bilaterian microRNAs in Platynereis dumerilii, a protostome retaining ancestral bilaterian features3,4, in Capitella, another marine annelid, in the sea urchin Strongylocentrotus, a deuterostome, and in sea anemone Nematostella, representing an outgroup to the bilaterians. Our comparative data indicate that the oldest known animal microRNA, miR-100, and the related miR-125 and let-7 were initially active in neurosecretory cells located around the mouth. Other sets of ancient microRNAs were first present in locomotor ciliated cells, specific brain centres, or, more broadly, one of four major organ systems: central nervous system, sensory tissue, musculature and gut. These findings reveal that microRNA evolution and the establishment of tissue identities were closely coupled in bilaterian evolution. Also, they outline a minimum set of cell types and tissues that existed in the protostome–deuterostome ancestor.

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Figure 1: Foregut-related expression of conserved microRNAs.
Figure 2: MicroRNAs expressed in locomotor ciliated cells.
Figure 3: Expression of brain-specific microRNAs.
Figure 4: MicroRNAs demarcating organ systems.

Accession codes

Data deposits

Sequences for Platynereis miRNA primary transcripts pri-miR-100/let-7, pri-miR-12/216 and pri-miR-183/263 were deposited in the GenBank database with accession numbers FJ838789.1, FJ838790.1 and GU224283, respectively.

References

  1. 1

    Grimson, A. et al. Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature 455, 1193–1197 (2008)

    ADS  CAS  Article  Google Scholar 

  2. 2

    Wheeler, B. M. et al. The deep evolution of metazoan microRNAs. Evol. Dev. 11, 50–68 (2009)

    CAS  Article  Google Scholar 

  3. 3

    Raible, F. et al. Vertebrate-type intron-rich genes in the marine annelid Platynereis dumerilii . Science 310, 1325–1326 (2005)

    ADS  CAS  Article  Google Scholar 

  4. 4

    Tessmar-Raible, K. et al. Conserved sensory-neurosecretory cell types in annelid and fish forebrain: insights into hypothalamus evolution. Cell 129, 1389–1400 (2007)

    CAS  Article  Google Scholar 

  5. 5

    Shkumatava, A., Stark, A., Sive, H. & Bartel, D. P. Coherent but overlapping expression of microRNAs and their targets during vertebrate development. Genes Dev. 23, 466–481 (2009)

    CAS  Article  Google Scholar 

  6. 6

    Reinhart, B. J. et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans . Nature 403, 901–906 (2000)

    ADS  CAS  Article  Google Scholar 

  7. 7

    Caygill, E. E. & Johnston, L. A. Temporal regulation of metamorphic processes in Drosophila by the let-7 and miR-125 heterochronic microRNAs. Curr. Biol. 18, 943–950 (2008)

    CAS  Article  Google Scholar 

  8. 8

    Sokol, N. S., Xu, P., Jan, Y. N. & Ambros, V. Drosophila let-7 microRNA is required for remodeling of the neuromusculature during metamorphosis. Genes Dev. 22, 1591–1596 (2008)

    CAS  Article  Google Scholar 

  9. 9

    Poy, M. N. et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432, 226–230 (2004)

    ADS  CAS  Article  Google Scholar 

  10. 10

    Wienholds, E. et al. MicroRNA expression in zebrafish embryonic development. Science 309, 310–311 (2005)

    ADS  CAS  Article  Google Scholar 

  11. 11

    Scholz, C. B. & Technau, U. The ancestral role of Brachyury: expression of NemBra1 in the basal cnidarian Nematostella vectensis (Anthozoa). Dev. Genes Evol. 212, 563–570 (2003)

    CAS  PubMed  Google Scholar 

  12. 12

    Arendt, D., Technau, U. & Wittbrodt, J. Evolution of the bilaterian larval foregut. Nature 409, 81–85 (2001)

    ADS  CAS  Article  Google Scholar 

  13. 13

    Nielsen, C. Animal Evolution: Interrelationships of the Living Phyla, 2nd edn (Oxford Univ. press, 2001)

    Google Scholar 

  14. 14

    Kapsimali, M. et al. MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system. Genome Biol. 8, R173 (2007)

    Article  Google Scholar 

  15. 15

    Deo, M. et al. Detection of mammalian microRNA expression by in situ hybridization with RNA oligonucleotides. Dev. Dyn. 235, 2538–2548 (2006)

    CAS  Article  Google Scholar 

  16. 16

    Farh, K. K. et al. The widespread impact of mammalian microRNAs on mRNA repression and evolution. Science 310, 1817–1821 (2005)

    ADS  CAS  Article  Google Scholar 

  17. 17

    Aboobaker, A. A. et al. Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development. Proc. Natl Acad. Sci. USA 102, 18017–18022 (2005)

    ADS  CAS  Article  Google Scholar 

  18. 18

    González-Estévez, C. et al. Diverse miRNA spatial expression patterns suggest important roles in homeostasis and regeneration in planarians. Int. J. Dev. Biol. (in the press) (2009)

  19. 19

    Denes, A. S. et al. Molecular architecture of annelid nerve cord supports common origin of nervous system centralization in bilateria. Cell 129, 277–288 (2007)

    CAS  Article  Google Scholar 

  20. 20

    Rao, P. K. et al. Myogenic factors that regulate expression of muscle-specific microRNAs. Proc. Natl Acad. Sci. USA 103, 8721–8726 (2006)

    ADS  CAS  Article  Google Scholar 

  21. 21

    Sood, P. et al. Cell-type-specific signatures of microRNAs on target mRNA expression. Proc. Natl Acad. Sci. USA 103, 2746–2751 (2006)

    ADS  CAS  Article  Google Scholar 

  22. 22

    Prochnik, S. E., Rokhsar, D. S. & Aboobaker, A. A. Evidence for a microRNA expansion in the bilaterian ancestor. Dev. Genes Evol. 217, 73–77 (2007)

    CAS  Article  Google Scholar 

  23. 23

    Szafranska, A. E. et al. MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene 26, 4442–4452 (2007)

    CAS  Article  Google Scholar 

  24. 24

    Pasquinelli, A. E. et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408, 86–89 (2000)

    ADS  CAS  Article  Google Scholar 

  25. 25

    Vigh, B. et al. The system of cerebrospinal fluid-contacting neurons. Its supposed role in the nonsynaptic signal transmission of the brain. Histol. Histopathol. 19, 607–628 (2004)

    CAS  PubMed  Google Scholar 

  26. 26

    Harada, Y. et al. Developmental expression of the hemichordate otx ortholog. Mech. Dev. 91, 337–339 (2000)

    CAS  Article  Google Scholar 

  27. 27

    Jékely, G. & Arendt, D. Cellular resolution expression profiling using confocal detection of NBT/BCIP precipitate by reflection microscopy. Biotechniques 42, 751–755 (2007)

    Article  Google Scholar 

  28. 28

    Rentzsch, F. et al. Asymmetric expression of the BMP antagonists chordin and gremlin in the sea anemone Nematostella vectensis: implications for the evolution of axial patterning. Dev. Biol. 296, 375–387 (2006)

    CAS  Article  Google Scholar 

  29. 29

    Arenas-Mena, C., Cameron, A. R. & Davidson, E. H. Spatial expression of Hox cluster genes in the ontogeny of a sea urchin. Development 127, 4631–4643 (2000)

    CAS  PubMed  Google Scholar 

  30. 30

    Pfeffer, S. et al. Identification of microRNAs of the herpesvirus family. Nature Methods 2, 269–276 (2005)

    CAS  Article  Google Scholar 

  31. 31

    Válóczi, A. et al. Sensitive and specific detection of microRNAs by northern blot analysis using LNA-modified oligonucleotide probes. Nucleic Acids Res. 32, e175 (2004)

    Article  Google Scholar 

  32. 32

    Wienholds, E. et al. MicroRNA expression in zebrafish embryonic development. Science 309, 310–311 (2005)

    ADS  CAS  Article  Google Scholar 

  33. 33

    Pall, G. S. & Hamilton, A. J. Improved northern blot method for enhanced detection of small RNA. Nature Protocols 3, 1077–1084 (2008)

    CAS  Article  Google Scholar 

  34. 34

    Griffiths-Jones, S., Saini, H. K., van Dongen, S. & Enright, A. J. miRBase: tools for microRNA genomics. Nucleic Acids Res. 36 (Database issue). D154–D158 (2008)

    CAS  Article  Google Scholar 

  35. 35

    Lu, J. et al. The birth and death of microRNA genes in Drosophila . Nature Genet. 40, 351–355 (2008)

    ADS  CAS  Article  Google Scholar 

  36. 36

    Morin, R. D. et al. Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. Genome Res. 18, 610–621 (2008)

    CAS  Article  Google Scholar 

  37. 37

    Hofacker, I. L. Vienna RNA secondary structure server. Nucleic Acids Res. 31, 3429–3431 (2003)

    CAS  Article  Google Scholar 

  38. 38

    Lewis, B. P., Burge, C. B. & Bartel, D. P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15–20 (2005)

    CAS  Article  Google Scholar 

  39. 39

    Kertesz, M. et al. The role of site accessibility in microRNA target recognition. Nature Genet. 39, 1278–1284 (2007)

    CAS  Article  Google Scholar 

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Acknowledgements

We thank A. Fischer for drawing schematic illustrations and providing probes for tropomyosin 1, A. Boutla for advice when initiating the project, J. Brennecke for help with small RNA cloning and discussions, M. Hentze for critical reading of the manuscript, P. Steinmetz and U. Technau for Nematostella embryos and discussions, E. Arboleda and I. Arnone for sea urchin plutei and discussions. V. Benes and the EMBL-Genecore facility for expert technical advice, W. R. McCombie, M. Rooks and E. Hodges for help with sequencing and M. Arumugam, V. Van Noort, J. Muller and C. Creevey for advice in target analysis.

Author Contributions F.C. initiated the project, cloned Platynereis small RNAs, characterized the temporal and spatial expression of ancient miRNAs and their targets, coordinated the collaborations and wrote the paper. F.R. analysed and evaluated the Solexa sequencing data. R.T. assembled the 3′UTRs of targets from Platynereis ESTs and provided riboprobes. O.S. did the SNP and miRNA::target co-expression analysis. K.T. performed target predictions under the supervision of P.B., and S.K characterized foxa2 expression. H.S. generated probes for targets in situ screen. G.J.H. hosted the small RNA cloning and sequencing. D.A. analysed comparative miRNA expression, provided ideas and strategies and wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Detlev Arendt.

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This file contains Supplementary Figures 1-8 with Legends, Supplementary Tables 1-6, Supplementary Data and Supplementary References. (PDF 1297 kb)

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Christodoulou, F., Raible, F., Tomer, R. et al. Ancient animal microRNAs and the evolution of tissue identity. Nature 463, 1084–1088 (2010). https://doi.org/10.1038/nature08744

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