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

Abstract

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.

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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.

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Acknowledgements

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.

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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.

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Correspondence to Yuji Kageyama.

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The authors declare no competing financial interests.

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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). https://doi.org/10.1038/ncb1595

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