Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-8448b6f56d-wq2xx Total loading time: 0 Render date: 2024-04-19T02:21:07.975Z Has data issue: false hasContentIssue false

4 - MicroRNAs: A small contribution from worms

Published online by Cambridge University Press:  31 July 2009

By
Amy E. Pasquinelli
Edited by
Krishnarao Appasani
Foreword by
Andrew Fire  and
Marshall Nirenberg
Amy E. Pasquinelli
Affiliation:
Molecular Biology Section, University of California
Krishnarao Appasani
Affiliation:
GeneExpression Systems, Inc., Massachusetts
Andrew Fire
Affiliation:
Stanford University, California
Get access

Summary

Introduction

The 2002 Nobel Prize for Medicine was awarded to Sydney Brenner, Robert Horvitz and John Sulston for their seminal work in establishing the nematode Caenorhabditis elegans as a model genetic organism for studying development and behavior. One of the most sensational discoveries to emerge from C. elegans is the identification of tiny, non-coding RNA genes that regulate development. The original report of a 22 nucleotide (nt) RNA essential for controlling temporal patterning in the worm was unprecedented. Seven years passed before another 22-nt RNA gene was found, once again through genetic studies of developmental timing in C. elegans. This second tiny RNA gene turned out not to be a worm oddity, but instead it was shown to be expressed in most animal species. Thus, the general existence of 22-nt RNA genes was established and the hunt for additional RNAs of this type intensified. Hundreds of ∼22-nt RNA genes have now been uncovered in plants and animals. It is not a coincidence that the tiny size of these endogenous RNAs, called microRNAs (miRNAs), is similar to that of the small interfering RNAs (siRNAs) that direct RNA interference (RNAi); common cellular factors and mechanisms participate in the expression and function of these ∼22-nt RNAs. This chapter focuses on how the discovery of 22-nt RNA genes in C. elegans revealed the broad existence of miRNAs and how the regulation of gene expression by miRNAs compares to RNAi.

Type
Chapter
Information
RNA Interference Technology
From Basic Science to Drug Development
 , pp. 69 - 83
Publisher: Cambridge University Press
Print publication year: 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abrahante, J. E., Daul, A. L., Li, M., Volk, M. L., Tennessen, J. M., Miller, E. A. and Rougvie, A. E. (2003). The Caenorhabditis elegans hunchback-like gene lin-57/hbl-1 controls developmental time and is regulated by microRNAs. Developmental Cell, 4, 625–637CrossRefGoogle ScholarPubMed
Ambros, V. and Horvitz, H. R. (1984). Heterochronic mutants of the nematode Caenorhabditis elegans. Science, 226, 409–416CrossRefGoogle ScholarPubMed
Ambros, V. and Horvitz, H. R. (1987). The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events. Genes & Development, 1, 398–414CrossRefGoogle ScholarPubMed
Ambros, V. (1989). A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans. Cell, 57, 49–57CrossRefGoogle ScholarPubMed
Ambros, V. (2001). microRNAs: Tiny regulators with great potential. Cell, 107, 823–826CrossRefGoogle ScholarPubMed
Ambros, V. (2003). microRNA pathways in flies and worms: Growth, death, fat, stress, and timing. Cell, 113, 673–676CrossRefGoogle Scholar
Ambros, V., Bartel, B., Bartel, D. P., Burge, C. B., Carrington, J. C., Chen, X., Dreyfuss, G., Eddy, S. R., Griffiths-Jones, S., Marshall, M., Matzke, M., Ruvkun, G. and Tuschl, T. (2003a). A uniform system for microRNA annotation. RNA, 9, 277–279CrossRefGoogle 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, 807–818CrossRefGoogle Scholar
Banerjee, D. and Slack, F. (2002). Control of developmental timing by small temporal RNAs: A paradigm for RNA-mediated regulation of gene expression. Bioessays, 24, 119–129CrossRefGoogle ScholarPubMed
Bashirullah, A., Pasquinelli, A. E., Kiger, A. A., Perrimon, N., Ruvkun, G. and Thummel, C. S. (2003). Coordinate regulation of small temporal RNAs at the onset of Drosophila metamorphosis. Developmental Biology, 259, 1–8CrossRefGoogle ScholarPubMed
Bernstein, E., Caudy, A. A., Hammond, S. M. and Hannon, G. J. (2001). Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature, 409, 363–366CrossRefGoogle ScholarPubMed
Bohmert, K., Camus, I., Bellini, C., Bouchez, D., Caboche, M. and Benning, C. (1998). AGO1 defines a novel locus of Arabidopsis controlling leaf development. European Molecular Biology Organization Journal, 17, 170–180CrossRefGoogle ScholarPubMed
Caplen, N. J., Fleenor, J., Fire, A. and Morgan, R. A. (2000). dsRNA-mediated gene silencing in cultured Drosophila cells: A tissue culture model for the analysis of RNA interference. Gene, 252, 95–105CrossRefGoogle ScholarPubMed
Carthew, R. W. (2001). Gene silencing by double-stranded RNA. Current Opinions in Cell Biology, 13, 244–248CrossRefGoogle ScholarPubMed
Cerutti, L., Mian, N. and Bateman, A. (2000). Domains in gene silencing and cell differentiation proteins: The novel PAZ domain and redefinition of the Piwi domain. Trends in Biochemical Sciences, 25, 481–482CrossRefGoogle ScholarPubMed
Chalfie, M., Horvitz, H. R. and Sulston, J. E. (1981). Mutations that lead to reiterations in the cell lineages of C. elegans. Cell, 24, 59–69CrossRefGoogle ScholarPubMed
Dennis, C. (2002). The brave new world of RNA. Nature, 418, 122–124CrossRefGoogle ScholarPubMed
Doench, J. G., Petersen, C. P. and Sharp, P. A. (2003). siRNAs can function as miRNAs. Genes & Development, 17, 438–442CrossRefGoogle ScholarPubMed
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. and Tuschl, T. (2001a). Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 411, 494–498CrossRefGoogle Scholar
Elbashir, S. M., Lendeckel, W. and Tuschl, T. (2001b). RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes & Development, 15, 188–200CrossRefGoogle Scholar
Elbashir, S. M., Martinez, J., Patkaniowska, A., Lendeckel, W. and Tuschl, T. (2001c). Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. European Molecular Biology Organization Journal, 20, 6877–6888CrossRefGoogle Scholar
Fagard, M., Boutet, S., Morel, J. B., Bellini, C. and Vaucheret, H. (2000). AGO1, QDE-2, and RDE-1 are related proteins required for post-transcriptional gene silencing in plants, quelling in fungi, and RNA interference in animals. Proceedings of the National Academy of Sciences USA, 97, 11650–11654CrossRefGoogle ScholarPubMed
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E. and Mello, C. C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 391, 806–811CrossRefGoogle ScholarPubMed
Grad, Y., Aach, J., Hayes, G. D., Reinhart, B. J., Church, G. M., Ruvkun, G. and Kim, J. (2003). Computational and experimental identification of C. elegans microRNAs. Molecular Cell, 11, 1253–1263CrossRefGoogle ScholarPubMed
Grishok, A., Pasquinelli, A. E., Conte, D., Li, N., Parrish, S., Ha, I., Baillie, D. L., Fire, A., Ruvkun, G. and Mello, C. C. (2001). Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell, 106, 23–34CrossRefGoogle ScholarPubMed
Grosshans, H. and Slack, F. J. (2002). Micro-RNAs: Small is plentiful. Journal of Cell Biology, 156, 17–21CrossRefGoogle Scholar
Ha, I., Wightman, B. and Ruvkun, G. (1996). A bulged lin-4/lin-14 RNA duplex is sufficient for Caenorhabditis elegans lin-14 temporal gradient formation. Genes & Development, 10, 3041–3050CrossRefGoogle ScholarPubMed
Hamilton, A. J. and Baulcombe, D. C. (1999). A species of small antisense RNA in posttranscriptional gene silencing in plants. Science, 286, 950–952CrossRefGoogle ScholarPubMed
Hammond, S. M., Bernstein, E., Beach, D. and Hannon, G. J. (2000). An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature, 404, 293–296CrossRefGoogle ScholarPubMed
Hunter, C. and Poethig, R. S. (2003). miSSING LINKS: miRNAs and plant development. Current Opinion in Genetics and Development, 13, 372–378CrossRefGoogle ScholarPubMed
Hüttenhofer, A., Brosius, J., Bachellerie, J.-P. (2003). RNomics: identification and function of small, non-messenger RNAs. Current Opinion in Chemical Biology, 6, 835–843CrossRefGoogle Scholar
Hütvagner, G., McLachlan, J., Pasquinelli, A. E., Balint, E., Tuschl, T. and Zamore, P. D. (2001). A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science, 293, 834–838CrossRefGoogle ScholarPubMed
Hütvagner, G. and Zamore, P. D. (2002). A microRNA in a multiple-turnover RNAi enzyme complex. Science, 297, 2056–2060CrossRefGoogle 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, 364–379CrossRefGoogle Scholar
Ketting, R. F., Fischer, S. E., Bernstein, E., Sijen, T., Hannon, G. J. and Plasterk, R. H. (2001). Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes & Development, 15, 2654–2659CrossRefGoogle ScholarPubMed
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, 2269–2271CrossRefGoogle ScholarPubMed
Lagos-Quintana, M., Rauhut, R., Lendeckel, W. and Tuschl, T. (2001). Identification of novel genes coding for small expressed RNAs. Science, 294, 853–858CrossRefGoogle ScholarPubMed
Lagos-Quintana, M., Rauhut, R., Yalcin, A., Meyer, J., Lendeckel, W. and Tuschl, T. (2002). Identification of tissue-specific microRNAs from mouse. Current Biology, 12, 735–739CrossRefGoogle ScholarPubMed
Lai, E. C. and Posakony, J. W. (1997). The Bearded box, a novel 3′ UTR sequence motif, mediates negative post-transcriptional regulation of Bearded and Enhancer of split Complex gene expression. Development, 124, 4847–4856Google ScholarPubMed
Lai, E. C., Burks, C. and Posakony, J. W. (1998). The K box, a conserved 3′ UTR sequence motif, negatively regulates accumulation of enhancer of split complex transcripts. Development, 125, 4077–4088Google Scholar
Lai, E. C. (2002). Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nature Genetics, 30, 363–364CrossRefGoogle ScholarPubMed
Lai, E. C., Tomancak, P., Williams, R. W. and Rubin, G. M. (2003). Computational identification of Drosophila microRNA genes. Genome Biology, 4, R42CrossRefGoogle ScholarPubMed
Lau, N. C., Lim, E. P., Weinstein, E. G. and Bartel, D. P. (2001). An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science, 294, 858–862CrossRefGoogle ScholarPubMed
Lee, R. C. and Ambros, V. (2001). An extensive class of small RNAs in Caenorhabditis elegans. Science, 294, 862–864CrossRefGoogle ScholarPubMed
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, 843–854CrossRefGoogle Scholar
Lee, Y., Jeon, K., Lee, J. T., Kim, S. and Kim, V. N. (2002). microRNA maturation: stepwise processing and subcellular localization. European Molecular Biology Organization Journal, 21, 4663–4670CrossRefGoogle ScholarPubMed
Lim, L. P., Glasner, M. E., Yekta, S., Burge, C. B. and Bartel, D. P. (2003a). Vertebrate microRNA genes. Science, 299, 1540CrossRefGoogle Scholar
Lim, L. P., Lau, N. C., Weinstein, E. G., Abdelhakim, A., Yekta, S., Rhoades, M. W., Burge, C. B. and Bartel, D. P. (2003b). The microRNAs of Caenorhabditis elegans. Genes & Development, 17, 991–1008CrossRefGoogle Scholar
Lin, S. Y., Johnson, S. M., Abraham, M., Vella, M. C., Pasquinelli, A., Gamberi, C., Gottlieb, E. and Slack, F. J. (2003). The C. elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target. Developmental Cell, 4, 639–650CrossRefGoogle Scholar
Llave, C., Xie, Z., Kasschau, K. D. and Carrington, J. C. (2002). Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science, 297, 2053–2056CrossRefGoogle ScholarPubMed
McManus, M. T., Petersen, C. P., Haines, B. B., Chen, J. and Sharp, P. A. (2002). Gene silencing using micro-RNA designed hairpins. RNA, 8, 842–850CrossRefGoogle ScholarPubMed
Moss, E. G., Lee, R. C. and Ambros, V. (1997). The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell, 88, 637–646CrossRefGoogle Scholar
Moss, E. G. and Poethig, R. S. (2002). microRNAs: Something new under the sun. Current Biology, 12, R688–690CrossRefGoogle ScholarPubMed
Moss, E. G. and Tang, L. (2003). Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites. Developmental Biology, 258, 432–442CrossRefGoogle ScholarPubMed
Mourelatos, Z., Dostie, J., Paushkin, S., Sharma, A., Charroux, B., Abel, L., Rappsilber, J., Mann, M. and Dreyfuss, G. (2002). miRNPs A novel class of ribonucleoproteins containing numerous microRNAs. Genes & Development, 16, 720–728CrossRefGoogle ScholarPubMed
Olsen, P. H. and Ambros, V. (1999). The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Developmental Biology, 216, 671–680CrossRefGoogle ScholarPubMed
Park, W., Li, J., Song, R., Messing, J. and Chen, X. (2002). CARPEL FACTORY, a Dicer homolog, and HEN1, a novel protein, act in microRNA metabolism in Arabidopsis thaliana. Current Biology, 12, 1484–1495CrossRefGoogle ScholarPubMed
Parrish, S., Fleenor, J., Xu, S., Mello, C. and Fire, A. (2000). Functional anatomy of a dsRNA trigger. Differential requirement for the two trigger strands in RNA interference. Molecular Cell, 6, 1077–1087CrossRefGoogle ScholarPubMed
Pasquinelli, A. E., Reinhart, B. J., Slack, F., Martindale, M. Q., Kuroda, M. I., Maller, B., Hayward, D. C., Ball, E. E., Degnan, B., Muller, P., Spring, J., Srinivasan, A., Fishman, M., Finnerty, J., Corbo, J., Levine, M., Leahy, P., Davidson, E. and Ruvkun, G. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature, 408, 86–89Google ScholarPubMed
Pasquinelli, A. E. (2002). microRNAs: Deviants no longer. Trends in Genetics, 18, 171–173CrossRefGoogle ScholarPubMed
Pasquinelli, A. E. and Ruvkun, G. (2002). Control of developmental timing by microRNAs and their targets. Annual Reviews of Cell and Developmental Biology, 18, 495–513CrossRefGoogle ScholarPubMed
Pasquinelli, A. E., McCoy, A., Jimenez, E., Salo, E., Ruvkun, G., Martindale, M. Q. and Baguna, J. (2003). Expression of the 22 nucleotide let-7 heterochronic RNA throughout the Metazoa: A role in life history evolution?Evolution & Development, 5, 372–378CrossRefGoogle ScholarPubMed
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, 901–906CrossRefGoogle ScholarPubMed
Reinhart, B. J., Weinstein, E. G., Rhoades, M. W., Bartel, B. and Bartel, D. P. (2002). microRNAs in plants. Genes & Development, 16, 1616–1626CrossRefGoogle ScholarPubMed
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, 313–319CrossRefGoogle ScholarPubMed
Ruvkun, G. (2001). Molecular biology. Glimpses of a tiny RNA world. Science, 294, 797–799CrossRefGoogle ScholarPubMed
Schwarz, D. S. and Zamore, P. D. (2002). Why do miRNAs live in the miRNP?Genes & Development, 16, 1025–1031CrossRefGoogle ScholarPubMed
Seggerson, K., Tang, L. and Moss, E. G. (2002). Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation. Developmental Biology, 243, 215–225CrossRefGoogle ScholarPubMed
Sempere, L. F., Sokol, N. S., Dubrovsky, E. B., Berger, E. M. and Ambros, V. (2003). Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and broad-Complex gene activity. Developmental Biology, 259, 9–18CrossRefGoogle ScholarPubMed
Slack, F. J. and Ruvkun, G. (1998). A novel repeat domain that is often associated with RING finger and B- box motifs. Trends Biochem Sci, 23, 474–475CrossRefGoogle ScholarPubMed
Slack, F. J., Basson, M., Liu, Z., Ambros, V., Horvitz, H. R. and Ruvkun, G. (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, 659–669CrossRefGoogle Scholar
Sulston, J. E. and Horvitz, H. R. (1977). Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Developmental Biology, 56, 110–156CrossRefGoogle ScholarPubMed
Sulston, J. E. and Horvitz, H. R. (1981). Abnormal cell lineages in mutants of the nematode Caenorhabditis elegans. Developmental Biology, 82, 41–55CrossRefGoogle ScholarPubMed
Tabara, H., Sarkissian, M., Kelly, W. G., Fleenor, J., Grishok, A., Timmons, L., Fire, A. and Mello, C. C. (1999). The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell, 99, 123–132CrossRefGoogle ScholarPubMed
Tuschl, T., Zamore, P. D., Lehmann, R., Bartel, D. P. and Sharp, P. A. (1999). Targeted mRNA degradation by double-stranded RNA in vitro. Genes & Development, 13, 3191–3197CrossRefGoogle ScholarPubMed
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, 855–862CrossRefGoogle ScholarPubMed
Yang, D., Lu, H. and Erickson, J. W. (2000). Evidence that processed small dsRNAs may mediate sequence-specific mRNA degradation during RNAi in Drosophila embryos. Current Biology, 10, 1191–1200CrossRefGoogle ScholarPubMed
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, 25–33CrossRefGoogle ScholarPubMed
Zamore, P. D. (2002). Ancient pathways programmed by small RNAs. Science, 296, 1265–1269CrossRefGoogle ScholarPubMed
Zeng, Y., Wagner, E. J. and Cullen, B. R. (2002). Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Molecular Cell, 9, 1327–1333CrossRefGoogle ScholarPubMed
Zeng, Y., Yi, R. and Cullen, B. R. (2003). microRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proceedings of the National Academy of Sciences U S A, 100, 9779–9784CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×