Abstract
Two small RNAs regulate the timing of Caenorhabditis elegans development1,2. Transition from the first to the second larval stage fates requires the 22-nucleotide lin-4 RNA1,3,4, and transition from late larval to adult cell fates requires the 21-nucleotide let-7 RNA2. The lin-4 and let-7 RNA genes are not homologous to each other, but are each complementary to sequences in the 3′ untranslated regions of a set of protein-coding target genes that are normally negatively regulated by the RNAs1,2,5,6. Here we have detected let-7 RNAs of ∼21 nucleotides in samples from a wide range of animal species, including vertebrate, ascidian, hemichordate, mollusc, annelid and arthropod, but not in RNAs from several cnidarian and poriferan species, Saccharomyces cerevisiae, Escherichia coli or Arabidopsis. We did not detect lin-4 RNA in these species. We found that let-7 temporal regulation is also conserved: let-7 RNA expression is first detected at late larval stages in C. elegans and Drosophila , at 48 hours after fertilization in zebrafish, and in adult stages of annelids and molluscs. The let-7 regulatory RNA may control late temporal transitions during development across animal phylogeny.
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References
Lee, R. C., Feinbaum, R. L. & Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843–854 ( 1993).
Reinhart, B. et al. The 21-nucleotide let-7 RNA regulates developmental timing in C. elegans. Nature 403, 901–906 (2000).
Chalfie, M., Horvitz, H. R. & Sulston, J. E. Mutations that lead to reiterations in the cell lineages of C. elegans. Cell 24, 59– 69 (1981).
Ambros, V. & Horvitz, H. R. The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events. Genes Dev. 1, 398– 414 (1987).
Wightman, B., Ha, I. & Ruvkun, G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75, 855–862 ( 1993).
Slack, F. et al. The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Mol. Cell 5, 659– 669 (2000).
Aguinaldo, A. M. et al. Evidence for a clade of nematodes, arthropods and other moulting animals. Nature 387, 489– 493 (1997).
Zamore, P. D., Tuschl, T., Sharp, P. A. & Bartel, D. P. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101, 25–33 (2000).
Hammond, S. M., Bernstein, E., Beach, D. & Hannon, G. J. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404, 293– 296 (2000).
Tuschl, T., Zamore, P. D., Lehmann, R., Bartel, D. P. & Sharp, P. A. Targeted mRNA degradation by double-stranded RNA in vitro. Genes Dev. 13, 3191 –3197 (1999).
Montgomery, M. K., Xu, S. & Fire, A. RNA as a target of double-stranded RNA-mediated genetic interference in Caenorhabiditis elegans. Proc. Natl Acad. Sci. USA 95, 15502–15507 (1998).
Fire, A. et al. Potent and specific genetic interference by double-stranded RNA in Caenorhbditis elegans. Nature 391, 806–810 (1998).
Olsen, P. H. & Ambros, V. 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, 671–680 (1999).
Tabara, H. et al. The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell 99, 123– 132 (1999).
Acknowledgements
We thank the following people for RNA and tissue samples: T. Heanue, R. Pearse and C. Tabin for chick; J. Gerhart and M. Kirschner for Xenopus and acorn worm; S. Agarwal for Xenopus; N. Stavropoulos for mouse; C. Unabia and K. del Carmen for annelid and mollusc; H. Bode for Hydra; J. Nardone and S. Ferrari for Arabidopsis; P. Sudarsanam for yeast; and D. Selinger for E. coli. The phylogenetic survey in this work was inspired by the NASA Evolution and Development meetings organized by E. Davidson and C. Golden. This work was supported by an NIH grant from NIGMS to G.R. and a grant from the MGH Fund for Medical Discovery to A.E.P.
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Pasquinelli, A., Reinhart, B., Slack, F. et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408, 86–89 (2000). https://doi.org/10.1038/35040556
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DOI: https://doi.org/10.1038/35040556
