Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Small peptide regulators of actin-based cell morphogenesis encoded by a polycistronic mRNA


Transcriptome analyses in eukaryotes, including mice and humans, have identified polyA-containing transcripts that lack long open reading frames (ORFs; >100 amino acids)1,2. These transcripts are believed most likely to function as non-coding RNAs, but their translational capacities and biological activities have not been characterized in detail. Here, we report that polished rice (pri), which was previously identified as a gene for a non-coding RNA in Drosophila3,4, is in fact transcribed into a polycistronic mRNA that contains evolutionarily conserved short ORFs that encode 11 or 32 amino acid-long peptides. pri was expressed in all epithelial tissues during embryogenesis. The loss of pri function completely eliminated apical cuticular structures, including the epidermal denticles and tracheal taenidia, and also caused defective tracheal-tube expansion. We found that pri is essential for the formation of specific F-actin bundles that prefigures the formation of the denticles and taenidium. We provide evidences that pri acts non-cell autonomously and that four of the conserved pri ORFs are functionally redundant. These results demonstrate that pri has essential roles in epithelial morphogenesis by regulating F-actin organization.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Expression pattern of MRE29 RNA during Drosophila embryogenesis.
Figure 2: polished rice is required for denticle formation.
Figure 3: Tracheal phenotypes of pri mutant embryos.
Figure 4: Polycistronic pri transcript encodes multiple small peptides.
Figure 5: PRI peptides are functionally redundant and act in a non-cell autonomous manner.


  1. Ota, T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature Genet. 36, 40–45 (2004).

    Article  Google Scholar 

  2. Carninci, P. et al. The transcriptional landscape of the mammalian genome. Science 309, 1559–1563 (2005).

    Article  CAS  Google Scholar 

  3. Tupy, J. L. et al. Identification of putative noncoding polyadenylated transcripts in Drosophila melanogaster. Proc. Natl Acad. Sci. USA 102, 5495–5500 (2005).

    Article  CAS  Google Scholar 

  4. Inagaki, S. et al. Identification and expression analysis of putative mRNA-like non-coding RNA in Drosophila. Genes Cells 10, 1163–1173 (2005).

    Article  CAS  Google Scholar 

  5. Delon, I., Chanut-Delalande, H. & Payre, F. The Ovo/Shavenbaby transcription factor specifies actin remodelling during epidermal differentiation in Drosophila. Mech. Dev. 120, 747–758 (2003).

    Article  CAS  Google Scholar 

  6. Price, M. H., Roberts, D. M., McCartney, B. M., Jezuit, E. & Peifer, M. Cytoskeletal dynamics and cell signaling during planar polarity establishment in the Drosophila embryonic denticle. J. Cell Sci. 119, 403–415 (2006).

    Article  CAS  Google Scholar 

  7. Walters, J. W., Dilks, S. A. & Dinardo, S. Planar polarization of the denticle field in the Drosophila embryo: roles for myosin II (zipper) and fringe. Dev. Biol. 297, 323–339 (2006).

    Article  CAS  Google Scholar 

  8. Kiehart, D. P., Galbraith, C. G., Edwards, K. A., Rickoll, W. L. & Montague, R. A. Multiple forces contribute to cell sheet morphogenesis for dorsal closure in Drosophila. J. Cell Biol. 149, 471–490 (2000).

    Article  CAS  Google Scholar 

  9. Payre, F., Vincent, A. & Carreno, S. ovo/svb integrates Wingless and DER pathways to control epidermis differentiation. Nature 400, 271–275 (1999).

    Article  CAS  Google Scholar 

  10. Shiga, Y., Tanaka-Matakatsu, M. & Hayashi, S. A nuclear GFP β-galactosidase fusion protein as a marker for morphogenesis in living Drosophila. Dev. Growth Differ. 38, 99–106 (1996).

    Article  CAS  Google Scholar 

  11. Matusek, T. et al. The Drosophila formin DAAM regulates the tracheal cuticle pattern through organizing the actin cytoskeleton. Development 133, 957–966 (2006).

    Article  CAS  Google Scholar 

  12. Chihara, T., Kato, K., Taniguchi, M., Ng, J. & Hayashi, S. Rac promotes epithelial cell rearrangement during tracheal tubulogenesis in Drosophila. Development 130, 1419–1428 (2003).

    Article  CAS  Google Scholar 

  13. Beitel, G. J. & Krasnow, M. A. Genetic control of epithelial tube size in the Drosophila tracheal system. Development 127, 3271–3282 (2000).

    CAS  PubMed  Google Scholar 

  14. Moussian, B., Soding, J., Schwarz, H. & Nusslein-Volhard, C. Retroactive, a membrane-anchored extracellular protein related to vertebrate snake neurotoxin-like proteins, is required for cuticle organization in the larva of Drosophila melanogaster. Dev. Dyn. 233, 1056–1063 (2005).

    Article  CAS  Google Scholar 

  15. Moussian, B. et al. Drosophila Knickkopf and Retroactive are needed for epithelial tube growth and cuticle differentiation through their specific requirement for chitin filament organization. Development 133, 163–171 (2006).

    Article  CAS  Google Scholar 

  16. Luschnig, S., Batz, T., Armbruster, K. & Krasnow, M. A. serpentine and vermiform encode matrix proteins with chitin binding and deacetylation domains that limit tracheal tube length in Drosophila. Curr. Biol. 16, 186–194 (2006).

    Article  CAS  Google Scholar 

  17. Savard, J., Marques-Souza, H., Aranda, M. & Tautz, D. A segmentation gene in tribolium produces a polycistronic mRNA that codes for multiple conserved peptides. Cell 126, 559–569 (2006).

    Article  CAS  Google Scholar 

  18. Chanut-Delalande, H., Fernandes, I., Roch, F., Payre, F. & Plaza, S. Shavenbaby couples patterning to epidermal cell shape control. PLoS Biol. 4, e290 (2006).

    Article  Google Scholar 

  19. Parks, A. L. et al. Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome. Nature Genet. 36, 288–292 (2004).

    Article  CAS  Google Scholar 

  20. Spradling, A. C. & Rubin, G. M. Transposition of cloned P elements into Drosophila germ line chromosomes. Science 218, 341–347 (1982).

    Article  CAS  Google Scholar 

  21. Bartoszewski, S. & Gibson, J. B. Injecting un-dechrionated eggs of Drosophila melanogaster under ethanol Drosophila Information Newsletter 14 (1994).

    Google Scholar 

  22. Stern, D. L. & Sucena, E. in Drosophila Protocols (eds Sullivan, W., Ashburner, M. & Hawley, R. S.) 601–615 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2000).

    Google Scholar 

  23. Nagaso, H., Murata, T., Day, N. & Yokoyama, K. K. Simultaneous detection of RNA and protein by in situ hybridization and immunological staining. J. Histochem. Cytochem. 49, 1177–1182 (2001).

    Article  CAS  Google Scholar 

  24. Patel, N. in Drosophila melanogaster: Practical Uses in Cell and Molecular Biology (ed. Lawrence S. B. Goldstein, E. A. F.) 445–488 (Academic Press, San Diego, 1995).

    Google Scholar 

  25. Brook, W. J. & Cohen, S. M. Antagonistic interactions between wingless and decapentaplegic responsible for dorsal-ventral pattern in the Drosophila Leg. Science 273, 1373–1377 (1996).

    Article  CAS  Google Scholar 

  26. Tonning, A. et al. A transient luminal chitinous matrix is required to model epithelial tube diameter in the Drosophila trachea. Dev. Cell 9, 423–430 (2005).

    Article  CAS  Google Scholar 

  27. Kondo, T., Inagaki, S., Yasuda, K. & Kageyama, Y. Rapid construction of Drosophila RNAi transgenes using pRISE, a P-element-mediated transformation vector exploiting an in vitro recombination system. Genes Genet. Syst. 81, 129–134 (2006).

    Article  CAS  Google Scholar 

Download references


We thank Y. Hiromi, A. Nakamura and K. Yasuda for critical comments and discussion. We also thank Bloomington and Kyoto Drosophila Stock Center, as well as National Institute of Genetics (Mishima, Japan) and Harvard Medical School, for kind supply of Drosophila strains. This work was supported by Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) to S.H. and Y.K.

Author information

Authors and Affiliations



T.K. was responsible for all aspects of experimental results. Y.H., K.K. and S.I. participated in genetical analysis of the mutant phenotype, time-lapse imaging and expression analysis, respectively. Y.K., S.H. and T.K. cowrote the paper. All coauthors disscussed the results and commented on the manuscript.

Corresponding author

Correspondence to Yuji Kageyama.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary figures S1, S2, S3, S4 and Supplementary methods (PDF 1730 kb)

Supplementary Information

Supplementary Movie 1 (MOV 4450 kb)

Supplementary Information

Supplementary Movie 2 (MOV 4050 kb)

Supplementary Information

Supplementary Movie 3 (MOV 2604 kb)

Supplementary Information

Supplementary Movie 4 (MOV 3634 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kondo, T., Hashimoto, Y., Kato, K. et al. Small peptide regulators of actin-based cell morphogenesis encoded by a polycistronic mRNA. Nat Cell Biol 9, 660–665 (2007).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing