let-7 RNA is first detected in late third instar (L3) larvae (Pasquinelli, 2000) around the time a pulse of the steroid hormone 20-hydroxyecdysone (ecdysone) triggers puparium formation (PF) and the onset of metamorphosis. To explore the potential influence of ecdysone on let-7 RNA expression, the profile of let-7 expression was determined during a period from late third larval instar, through prepupal development (a period marked by the sequential expression of ecdysone-inducible genes), to the adult stage. let-7 RNA is first detected at low levels around 4 h before PF. This stage coincides with a short period of high ecdysone titer that triggers PF. let-7 RNA remains at low levels during prepupal development, and then rapidly accumulates to high levels throughout pupal development, reaching a maximum of expression during the second day of pupal life. This rise in let-7 RNA parallels a prolonged pulse of high-level ecdysone secretion. This correlation between the profile of let-7 expression and the time course of changes in ecdysone titer suggests that ecdysone could induce let-7 transcription (Sempere, 2002).
The tissue-specificity of let-7 expression was determined in prepupae and adult animals in order to correlate expression domains with function. Tanning prepupae (0-4 h after PF) were dissected to obtain a variety of tissues: brains, imaginal discs, fat bodies, salivary glands, and Malphigian tubules. Levels of let-7 RNA in these tissues were quantified by Northern analysis. let-7 RNA was detected in all tissues examined, though at relatively higher levels in fat bodies and imaginal discs. The widespread expression of let-7 RNA suggests that let-7 could mediate diverse metamorphic processes, such as the terminal differentiation of imaginal discs and apoptosis of salivary glands and fat bodies. Levels of let-7 RNA in adult ovaries and carcasses (tissues remaining after ovary dissection) were quantified by Northern analysis. let-7 is expressed in both somatic and gonadal tissues in the adult (Sempere, 2002).
Abbott, A. L., et al. (2005). The let-7 microRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans. Dev. Cell 9: 403-414. 16139228
Abrahante, J. E., et al. (2003). The Caenorhabditis elegans hunchback-like Gene lin-57/hbl-1 controls developmental time and is regulated by microRNAs. Developmental Cell 4: 625-637. 12737799
Ashburner, M., Chihara, C., Meltzer, P. and Richards, G. (1974). Temporal control of puffing activity in polytene chromosomes. Cold Spring Harbor Symp. Quant. Biol. 38: 655-662. 4208797
Bashirullah, A., et al. (2003). Coordinate regulation of small temporal RNAs at the onset of Drosophila metamorphosis. Dev. Biol. 259: 1-8. 12812783
Basyuk, E., Suavet, F., Doglio, A., Bordonne, R. and Bertrand, E. (2003). Human let-7 stem-loop precursors harbor features of RNase III cleavage products. Nucleic Acids Res. 31(22): 6593-7. 14602919
Caudy, A. A., et al. (2003). A micrococcal nuclease homologue in RNAi effector complexes. Nature 425(6956): 411-414. 14508492
Forstemann, K., Tomari, Y., Du, T., Vagin, VV., Denli, A. M., Bratu, D. P., Klattenhoff, C., Theurkauf, W. E. and Zamore, P. D. (2005). Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein. PLoS Biol. 3(7): e236. 15918770
Garen, A., Kauvar, L., and Lepesant, J. A. (1977). Roles of ecdysone in Drosophila development. Proc. Natl. Acad. 74: 5099-5103
Grishok, A., et al. (2001). Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106(1): 23-34. 11461699
Grosshans, H., Johnson, T., Reinert, K. L., Gerstein, M. and Slack, F. J. (2005). The temporal patterning microRNA let-7 regulates several transcription factors at the larval to adult transition in C. elegans. Dev. Cell 8(3): 321-30. 15737928
Hayes, G. D., Frand, A. R. and Ruvkun, G. (2006). The mir-84 and let-7 paralogous microRNA genes of Caenorhabditis elegans direct the cessation of molting via the conserved nuclear hormone receptors NHR-23 and NHR-25. Development 133(23): 4631-41. Medline abstract: 17065234
Hutvagner, G., et al. (2001). A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293: 834-838. 11452083
Johnson, S. M., Lin, S.-Y. and Slack, F. J. (2003). The time of appearance of the C. elegans let-7 microRNA is transcriptionally controlled utilizing a temporal regulatory element in its promoter. Dev. Biol. 259: 364-379. 12871707
Ketting, R. F., et al. (2001). Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans Genes Dev. 15: 2654-2659. 11641272
Lagos-Quintana, M., et al. (2001). Identification of novel genes coding for small expressed RNAs. Science 294(5543): 853-858. 11679670
Lall, S., et al. (2006). A genome-wide map of conserved microRNA targets in C. elegans. Curr. Biol. 16(5): 460-71. Medline abstract: 16458514
Lee, R. C., Feinbaum, R. L., and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75: 843-854. 8252621
Lee, Y. S. and Dutta, A. (2007). The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 21: 1025-1030. Medline abstract: 17437991
Li, M., et al. (2005). Regulatory mutations of mir-48, a C. elegans let-7 family microRNA, cause developmental timing defects. Dev. Cell 9: 415-422. 16139229
Lin, S.-Y., et al. (2003). The C. elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microrna target. Dev. Cell 4: 639-650. 12737800
Pasquinelli, A. E., et al. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408(6808): 86-9. 11081512
Pepper, A. S.-R., et al. (2004). The C. elegans heterochronic gene lin-46 affects developmental timing at two larval stages and encodes a relative of the scaffolding protein gephyrin. Development 131: 2049-2059. 15073154
Pillai, R. S., et al. (2005). Inhibition of translational initiation by let-7 microRNA in human cells. Science 309(5740): 1573-6. 16081698
Reinhart, B. J., Slack, F. J., Basson, M., Pasquinelli, A. E., Bettinger, J. C., Rougvie, A. E., Horvitz, H. R., and Ruvkun, G. (2000). The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403: 901-906. 10706289
Saito, K., Ishizuka, A., Siomi, H., Siomi, M. C. (2005). Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells .PLoS Biol. 3(7): e235. 15918769
Slack, F. J., et al. (2000). 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. 10882102
Sempere, L. F., Dubrovsky, E. B., Dubrovskaya, V. A., Berger, E. M. and Ambros, V. (2002). The Expression of the let-7 small regulatory RNA is controlled by ecdysone during metamorphosis in Drosophila melanogaster. Dev. Biol. 244: 170-179. 11900466
Sempere, L. F., et al. (2003). Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and Broad-Complex gene activity. Dev. Biol. 259: 9-18. 12812784
date revised: 25 June 2007
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