The microRNAs of <span class='italic'>C. elegans</span>

doi:10.1017/CBO9780511541766.004

1 - The microRNAs of C. elegans

from I - Discovery of microRNAs in various organisms

Published online by Cambridge University Press: 22 August 2009

Ines Alvarez-Garcia and

Eric A. Miska

Edited by

Krishnarao Appasani

Foreword by

Sidney Altman and

Victor R. Ambros

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Ines Alvarez-Garcia: Affiliation:
The Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Biochemistry, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road Cambridge CB2 1QN, United Kingdom
Eric A. Miska: Affiliation:
The Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Biochemistry, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road Cambridge CB2 1QN, United Kingdom

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Summary

Discovery

MicroRNA (miRNA) is a class of short non-coding RNA that regulates gene expression in many eukaryotes. MicroRNA was first discovered in Caenorhabditis elegans by Victor Ambros' laboratory in 1993 (Lee et al., 1993). At the same time Gary Ruvkun's laboratory identified the first microRNA target gene (Wightman et al., 1993). Together, these two seminal discoveries identified a novel mechanism of post-transcriptional gene regulation. The history of these events has been reported recently, as remembered by the main researchers involved (Lee et al., 2004; Ruvkun et al., 2004). The realization of the importance of the discovery of microRNA, however, took about seven years and was preceded by the identification of a second microRNA in C. elegans by the Ruvkun and Horvitz laboratories and also by the rise in interest in another class of short RNA, siRNA, involved in the process of RNAi and related phenomena in plants and animals (Hamilton and Baulcombe, 1999; Zamore et al., 2000). Although the discovery of microRNA was unexpected, theoretical work on the mechanism of the lac repressor by Jacob and Monod had postulated a microRNA-like mechanism forty years earlier, see Figure 1.1 (Jacob and Monod, 1961).

Biogenesis and mechanism of action

From studies in C. elegans, Drosophila melanogaster and mammalian cell culture a model for microRNA biogenesis in animals is emerging (see Figure 1.2a and Figure 1.2b): microRNAs are transcribed by RNA polymerase II as long RNA precursors (pri-miRNAs) (Kim, 2005), which are processed in the nucleus by the RNase III enzyme Drosha and DGCR8/Pasha, to form the approximately 70 base pre-miRNA (Lee et al., 2003; Denli et al., 2004; Gregory et al., 2004; Han et al., 2004; Landthaler et al., 2004).

Type: Chapter
Information: MicroRNAs
From Basic Science to Disease Biology
, pp. 7 - 21

DOI: https://doi.org/10.1017/CBO9780511541766.004 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2007

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References

Abbott, A. L., Alvarez-Saavedra, E., Miska, E. A.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. Developmental Cell, 9, 403–414.Google Scholar

Abrahante, J. E., Daul, A. L., Li, M.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.Google Scholar

Ambros, V. (1989). A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans. Cell, 57, 49–57.Google Scholar

Ambros, V. and Horvitz, H. R. (1984). Heterochronic mutants of the nematode Caenorhabditis elegans. Science, 226, 409–416.Google Scholar

Ambros, V., Bartel, B., Bartel, D. P.et al. (2003a). A uniform system for microRNA annotation. RNA, 9, 277–279.Google Scholar

Ambros, V., Lee, R. C., Lavanway, A., Williams, P. T., and Jewell, D. (2003b). MicroRNAs and other tiny endogenous RNAs in C. elegans. Current Biology, 13, 807–818.Google Scholar

Antebi, A., Culotti, J. G. and Hedgecock, E. M. (1998). daf-12 regulates developmental age and the dauer alternative in Caenorhabditis elegans. Development, 125, 1191–1205.Google Scholar

Bagga, S., Bracht, J., Hunter, S.et al. (2005). Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell, 122, 553–563.Google Scholar

Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281–297.Google Scholar

Baugh, L. R. and Sternberg, P. W. (2006). DAF-16/FOXO regulates transcription of cki-1/Cip/Kip and repression of lin-4 during C. elegans L1 arrest. Current Biology, 16, 780–785.Google Scholar

Beitel, G. J., Clark, S. G. and Horvitz, H. R. (1990). Caenorhabditis elegans ras gene let-60 acts as a switch in the pathway of vulval induction. Nature, 348, 503–509.Google Scholar

Boehm, M. and Slack, F. (2005). A developmental timing microRNA and its target regulate life span in C. elegans. Science, 310, 1954–1957.Google Scholar

Brennecke, J., Hipfner, D. R., Stark, A., Russell, R. B. and Cohen, S. M. (2003). bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell, 113, 25–36.Google Scholar

Brennecke, J., Stark, A., Russell, R. B. and Cohen, S. M. (2005). Principles of microRNA-target recognition. Public Library of Science Biology, 3, e85.Google Scholar

Chalfie, M., Horvitz, H. R. and Sulston, J. E. (1981). Mutations that lead to reiterations in the cell lineages of C. elegans. Cell, 24, 59–69.Google Scholar

Chang, S., Johnston, R. J. Jr. and Hobert, O. (2003). A transcriptional regulatory cascade that controls left/right asymmetry in chemosensory neurons of C. elegans. Genes & Development, 17, 2123–2137.Google Scholar

Chang, S., Johnston, R. J., Frokjaer-Jensen, C.Jr., Lockery, S. and Hobert, O. (2004). MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode. Nature, 430, 785–789.Google Scholar

Cox, G. N., Staprans, S. and Edgar, R. S. (1981). The cuticle of Caenorhabditis elegans. II. Stage-specific changes in ultrastructure and protein composition during postembryonic development. Developmental Biology, 86, 456–470.Google Scholar

Denli, A. M., Tops, B. B., Plasterk, R. H., Ketting, R. F. and Hannon, G. J. (2004). Processing of primary microRNAs by the Microprocessor complex. Nature, 432, 231–235.Google Scholar

Du, T. and Zamore, P. D. (2005). microPrimer: the biogenesis and function of microRNA. Development, 132, 4645–4652.Google Scholar

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

Giraldez, A. J., Mishima, Y., Rihel, J.et al. (2006). Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science, 312, 75–79.Google Scholar

Gould, S. J. (2000). Of coiled oysters and big brains: how to rescue the terminology of heterochrony, now gone astray. Evolution & Development, 2, 241–248.Google Scholar

Grad, Y., Aach, J., Hayes, G. D.et al. (2003). Computational and experimental identification of C. elegans microRNAs. Molecular Cell, 11, 1253–1263.Google Scholar

Gregory, R. I., Yan, K. P., Amuthan, G.et al. (2004). The Microprocessor complex mediates the genesis of microRNAs. Nature, 432, 235–240.Google Scholar

Griffiths-Jones, S. (2004). The microRNA Registry. Nucleic Acids Research, 32, D109–111.Google Scholar

Griffiths-Jones, S., Grocock, R. J., Dongen, S., Bateman, A. and Enright, A. J. (2006). miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Research, 34, D140–144.Google Scholar

Grishok, A., Pasquinelli, A. E., Conte, D.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, 23–34.Google Scholar

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. Developmental Cell, 8, 321–330.Google Scholar

Hamilton, A. J. and Baulcombe, D. C. (1999). A species of small antisense RNA in posttranscriptional gene silencing in plants. Science, 286, 950–952.Google Scholar

Han, J., Lee, Y., Yeom, K. H.et al. (2004). The Drosha-DGCR8 complex in primary microRNA processing. Genes & Development, 18, 3016–3027.Google Scholar

Hobert, O., Johnston, R. J. Jr. and Chang, S. (2002). Left-right asymmetry in the nervous system: the Caenorhabditis elegans model. Nature Reviews Neuroscience, 3, 629–640.Google Scholar

Horvitz, H. R. and Sulston, J. E. (1980). Isolation and genetic characterization of cell-lineage mutants of the nematode Caenorhabditis elegans. Genetics, 96, 435–454.Google Scholar

Jacob, F. and Monod, J. (1961). Genetic regulatory mechanisms in the synthesis of proteins. Journal of Molecular Biology, 3, 318–356.Google Scholar

Jing, Q., Huang, S., Guth, S.et al. (2005). Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell, 120, 623–634.Google Scholar

John, B., Enright, A. J., Aravin, A.et al. (2004). Human microRNA targets. Public Library of Science Biology, 2, e363.Google Scholar

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. Developmental Biology, 259, 364–379.Google Scholar

Johnson, S. M., Grosshans, H., Shingara, J.et al. (2005). RAS is regulated by the let-7 microRNA family. Cell, 120, 635–647.Google Scholar

Johnston, R. J. and Hobert, O. (2003). A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature, 426, 845–849.Google Scholar

Ketting, R. F., Fischer, S. E., Bernstein, E.et al. (2001). Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes & Development, 15, 2654–2659.Google Scholar

Kidner, C. A. and Martienssen, R. A. (2004). Spatially restricted microRNA directs leaf polarity through ARGONAUTE1. Nature, 428, 81–84.Google Scholar

Kim, V. N. (2005). MicroRNA biogenesis: coordinated cropping and dicing. Nature Reviews Molecular Cell Biology, 6, 376–385.Google Scholar

Knight, S. W. and Bass, B. L. (2001). A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science, 293, 2269–2271.Google Scholar

Krichevsky, A. M., King, K. S., Donahue, C. P., Khrapko, K. and Kosik, K. S. (2003). A microRNA array reveals extensive regulation of microRNAs during brain development. RNA, 9, 1274–1281.Google Scholar

Lall, S., Grun, D., Krek, A.et al. (2006). A genome-wide map of conserved microRNA targets in C. elegans. Current Biology, 16, 460–471.Google Scholar

Landthaler, M., Yalcin, A. and Tuschl, T. (2004). The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis. Current Biology, 14, 2162–2167.Google Scholar

Lau, N. C., Lim, L. P., Weinstein, E. G. and Bartel, D. P. (2001). An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science, 294, 858–862.Google Scholar

Lee, R. C. and Ambros, V. (2001). An extensive class of small RNAs in Caenorhabditis elegans. Science, 294, 862–864.Google Scholar

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.Google Scholar

Lee, R., Feinbaum, R. and Ambros, V. (2004). A short history of a short RNA. Cell, 116, S89–92, 81 p following S96.Google Scholar

Lee, R. C., Hammell, C. M. and Ambros, V. (2006). Interacting endogenous and exogenous RNAi pathways in Caenorhabditis elegans. RNA, 4, 589–597.Google Scholar

Lee, Y., Ahn, C., Han, J.et al. (2003). The nuclear RNase III Drosha initiates microRNA processing. Nature, 425, 415–419.Google Scholar

Lewis, B. P., Shih, I. H., Jones-Rhoades, M. W., Bartel, D. P. and Burge, C. B. (2003). Prediction of mammalian microRNA targets. Cell, 115, 787–798.Google Scholar

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

Li, M., Jones-Rhoades, M. W., Lau, N. C., Bartel, D. P. and Rougvie, A. E. (2005). Regulatory mutations upstream of mir-48, a C. elegans let-7 family microRNA, cause developmental timing defects. Developmental Cell, 3, 415–422.Google Scholar

Lim, L. P., Lau, N. C., Weinstein, E. G.et al. (2003). The microRNAs of Caenorhabditis elegans. Genes & Development, 17, 991–1008.Google Scholar

Lin, S. Y., Johnson, S. M., Abraham, M.et al. (2003). The C. elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target. Developmental Cell, 4, 639–650.Google Scholar

Lund, E., Guttinger, S., Calado, A., Dahlberg, J. E. and Kutay, U. (2004). Nuclear export of microRNA precursors. Science, 303(5654), 95–98.Google Scholar

Mansfield, J. H., Harfe, B. D., Nissen, R.et al. (2004). MicroRNA-responsive ‘sensor’ transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nature Genetics, 36, 1079–1083.Google Scholar

Miska, E. A., Alvarez-Saavedra, E., Townsend, M.et al. (2004). Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biology, 5, R68.Google Scholar

Ohler, U., Yekta, S., Lim, L. P., Bartel, D. P. and Burge, C. B. (2004). Patterns of flanking sequence conservation and a characteristic upstream motif for microRNA gene identification. RNA, 10, 1309–1322.Google Scholar

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

Pillai, R. S., Bhattacharyya, S. N., Artus, C. G.et al. (2005). Inhibition of translational initiation by let-7 microRNA in human cells. Science, 309, 1573–1576.Google Scholar

Rajewsky, N. and Socci, N. D. (2004). Computational identification of microRNA targets. Developmental Biology, 267, 529–535.Google Scholar

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

Rougvie, A. E. (2005). Intrinsic and extrinsic regulators of developmental timing: from miRNAs to nutritional cues. Development, 132, 3787–3798.Google Scholar

Ruvkun, G. and Giusto, J. (1989). The Caenorhabditis elegans heterochronic gene lin-14 encodes a nuclear protein that forms a temporal developmental switch. Nature, 338, 313–319.Google Scholar

Ruvkun, G., Wightman, B. and Ha, I. (2004). The 20 years it took to recognize the importance of tiny RNAs. Cell, 116, S93–96, 92 p following S96.Google Scholar

Slack, F. J., Basson, M., Liu, Z.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. Molecular Cell, 5, 659–669.Google Scholar

Sokol, N. S. and Ambros, V. (2005). Mesodermally expressed Drosophila microRNA-1 is regulated by Twist and is required in muscles during larval growth. Genes & Development, 19, 2343–2354.Google Scholar

Stark, A., Brennecke, J., Russell, R. B. and Cohen, S. M. (2003). Identification of Drosophila microRNA targets. Public Library of Science Biology, 3, E60.Google Scholar

Stark, A., Brennecke, J., Bushati, N., Russell, R. B. and Cohen, S. M. (2005). Animal microRNAs confer robustness to gene expression and have a significant impact on 3′UTR evolution. Cell, 123, 1133–1146.Google Scholar

Sulston, J. E. and Horvitz, H. R. (1977). Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Developmental Biology, 56, 110–156.Google Scholar

Watanabe, Y., Yachie, N., Numata, K.et al. (2006). Computational analysis of microRNA targets in Caenorhabditis elegans. Gene, 365, 2–10.Google Scholar

Wienholds, E., Kloosterman, W. P., Miska, E.et al. (2005). MicroRNA expression in zebrafish embryonic development. Science, 309, 310–311.Google Scholar

Wightman, B., Ha, I. and Ruvkun, G. (1993). Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell, 75, 855–862.Google Scholar

Xie, X., Lu, J., Kulbokas, E. J.et al. (2005). Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals. Nature, 434, 338–345.Google Scholar

Yekta, S., Shih, I. H. and Bartel, D. P. (2004). MicroRNA-directed cleavage of HOXB8 mRNA. Science, 304, 594–596.Google Scholar

Yoo, A. S. and Greenwald, I. (2005). LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans. Science, 310, 1330–1333.Google Scholar

Zamore, P. D., Tuschl, T., Sharp, P. A. and Bartel, D. P. (2000). RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell, 101, 25–33.Google Scholar

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1 - The microRNAs of C. elegans

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