This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
References
Sulston, J.E., Schierenberg, E., White, J.G. & Thomson, J.N. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev. Biol. 100, 64–119 (1983).
Sulston, J.E. & Horvitz, H.R. Abnormal cell lineages in mutants of the nematode Caenorhabditis elegans. Dev. Biol. 82, 41–55 (1981).
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. Heterochronic mutants of the nematode Caenorhabditis elegans. Science 226, 409–416 (1984).
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).
Ambros, V. A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans. Cell 57, 49–57 (1989).
Ruvkun, G. et al. Molecular genetics of the Caenorhabditis elegans heterochronic gene lin-14. Genetics 121, 501–516 (1989).
Ruvkun, G. & Giusto, J. The Caenorhabditis elegans heterochronic gene lin-14 encodes a nuclear protein that forms a temporal switch during development. Nature 338, 313–319 (1989).
Wightman, B., Bürglin, T.R., Gatto, J., Arasu, P. & Ruvkun, G. Negative regulatory sequences in the lin-14 3′-untranslated region are necessary to generate a temporal switch during C. elegans development. Genes Dev. 5, 1813–1824 (1991).
Arasu, P., Wightman, B. & Ruvkun, G. Temporal regulation of lin-14 by the antagonistic action of two other heterochronic genes, lin-4 and lin-28. Genes Dev. 5, 1825–1833 (1991).
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).
Wightman, B., Ha, I. & Ruvkun, G. Post-transcriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75, 855–862 (1993).
Ha, I., Wightman, B. & Ruvkun, G. A bulged lin-4/lin-14 RNA duplex is sufficient for Caenorhabditis elegans lin-14 temporal gradient formation. Genes Dev. 10, 3041–3050 (1996).
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).
Reinhart, B.J. et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403, 901–906 (2000).
Slack, F.J. 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).
Pasquinelli, A.E. et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408, 86–89 (2000).
Lee, R.C. & Ambros, V. An extensive class of small RNAs in Caenorhabditis elegans. Science 294, 862–864 (2001).
Lagos-Quintana, M., Rauhut, R., Lendeckel, W. & Tuschl, T. Identification of novel genes coding for small expressed RNAs. Science 294, 853–858 (2001).
Lau, N.C., Lim, L.P., Weinstein, E.G. & Bartel, D.P. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294, 858–862 (2001).
Grad, Y. et al. Computational and experimental identification of C. elegans microRNAs. Mol. Cell 11, 1253–1263 (2003).
Klattenhoff, C. & Theurkauf, W. Biogenesis and germline functions of piRNAs. Development 135, 3–9 (2008).
Hamilton, A.J. & Baulcombe, D.C. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286, 950–952 (1999).
Elbashir, S.M., Lendeckel, W. & Tuschl, T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 15, 188–200 (2001).
Grishok, A. et al. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106, 23–34 (2001).
Hutvágner, G. et al. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293, 834–838 (2001).
Brodersen, P. et al. Widespread translational inhibition by plant miRNAs and siRNAs. Science 320, 1185–1190 (2008).
Chen, X. A microRNA as a translational repressor of APETALA2 in Arabidopsis flower development. Science 303, 2022–2025 (2004).
Carrington, J.C. & Ambros, V. Role of microRNAs in plant and animal development. Science 301, 336–338 (2003).
Parry, D.H., Xu, J. & Ruvkun, G. A whole-genome RNAi screen for C. elegans miRNA pathway genes. Curr. Biol. 17, 2013–2022 (2007).
Kim, J.K. et al. Functional genomic analysis of RNA interference in C. elegans. Science 308, 1164–1167 (2005).
Kennedy, S., Wang, D. & Ruvkun, G. A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans. Nature 427, 645–649 (2004).
Wang, D. et al. Somatic misexpression of germline P granules and enhanced RNA interference in C. elegans retinoblastoma pathway mutants. Nature 436, 593–597 (2005).
Fischer, S.E.J., Butler, M.D., Pan, Q. & Ruvkun, G. RNA duplex–mediated trans-splicing between independent mRNAs generates C. elegans ERI-6/7, a helicase that regulates RNAi. Nature (in the press).
Valadi, H. et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654–659 (2007).
Blower, M.D., Feric, E., Weis, K. & Heald, R. Genome-wide analysis demonstrates conserved localization of messenger RNAs to mitotic microtubules. J. Cell Biol. 179, 1365–1373 (2007).
Buhtz, A., Springer, F., Chappell, L., Baulcombe, D.C. & Kehr, J. Identification and characterization of small RNAs from the phloem of Brassica napus. Plant J. 53, 739–749 (2008).
Jacobsen, S.E., Running, M.P. & Meyerowitz, E.M. Disruption of an RNA helicase/RNAse III gene in Arabidopsis causes unregulated cell division in floral meristems. Development 126, 5231–5243 (1999).
Moss, E.G., Lee, R.C. & Ambros, V. The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell 88, 637–646 (1997).
Viswanathan, S.R., Daley, G.Q. & Gregory, R.I. Selective blockade of microRNA processing by Lin28. Science 320, 97–100 (2008).
Newman, M.A., Thomson, J.M. & Hammond, S.M. Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing. RNA 14, 1539–1549 (2008).
Richards, M., Tan, S.P., Tan, J.H., Chan, W.K. & Bongso, A. The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells 22, 51–64 (2004).
Yu, J. et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917–1920 (2007).
Motamedi, M.R. et al. Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119, 789–802 (2004).
Cogoni, C. & Macino, G. Gene silencing in Neurospora crassa requires a protein homologous to RNA-dependent RNA polymerase. Nature 399, 166–169 (1999).
Mochizuki, K., Fine, N.A., Fujisawa, T. & Gorovsky, M.A. Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in Tetrahymena. Cell 110, 689–699 (2002).
Ngo, H., Tschudi, C., Gull, K. & Ullu, E. Double-stranded RNA induces mRNA degradation in Trypanosoma brucei. Proc. Natl. Acad. Sci. USA 95, 14687–14692 (1998).
Acknowledgements
Most important to the discoveries described here were the fantastic students, postdocs, technical, and administrative staff who created the lab. I would like to express my deepest gratitude to B. Wightman, I. Ha, P. Arasu, J. Giusto, J. Gatto, T. Burglin, B. Reinhart, A. Pasquinelli, F. Slack, S. Kennedy, D. Wang, J. Kim, H. Gabel, R. Kamath, S. Fischer, M. Butler, D. Parry, G. Hayes, X. Wu, C. Zhang, S. Garcia, C. Phillips and S. Curran on the tiny RNA team. An equal number of people on the aging, metabolism and Mars projects also contributed deeply to the intellectual and technical growth of the lab. I launched my lab in the Department of Molecular Biology at Massachusetts General Hospital under very special circumstances: we were completely funded by Hoechst from 1985 to 1992 and almost half funded by them for another decade. This level of patronage allowed us to embark on the study of an array of experimental problems that would have been much more difficult to tackle in a traditional grant-funded environment. H. Goodman deserves very special thanks for his decision to broaden this Hoechst-funded research beyond the endocrinology that was probably their original intent, and for his shrewd recruiting in so many fields. And I thank P. Leder for founding and settling the Department of Genetics at Harvard, my academic home, and my colleagues in the Department of Molecular Biology at Massachusetts General Hospital and the Department of Genetics at Harvard who taught me how to run a lab by their many examples of discovery and training of great scientists. I arrived at graduate school greener than green in 1976, and it was a combination of my fellow students, D. Hanahan, V. Sundaresan, W. Herr, G. Church and T. Wu, and my teachers, F. Ausubel, W. Gilbert, and R. Horvitz, who showed me how to become a scientist. During my postdoc, V. Ambros was my developmental genetics teacher and collaborator extraordinaire, our collaboration now extending over a career, and M. Finney was also a close collaborator, which extended to his postdoctoral work in my lab and current co-direction of our search for extraterrestrial genomes (SETG). So the tribes of my education, my lab and my academic environment were uniquely inspiring, supportive, and loads of fun. But my home tribe has been the wellspring of strength and joy: Natasha Staller is presumably the most sophisticated molecular geneticist among the world's art historians. As a historian of Cubism, she can see cultural inflection points that most do not, and after years of asking me about many details of our work, and reading most of our papers, she is also a very sophisticated biologist. From this vantage point, Natasha nudged me towards ambitious, high-risk projects, and her confidence in my abilities, and in the talents of my students and postdocs, incited a certain boldness. And I am truly grateful to Natasha and to our daughter Victoria for the joyous home life of our little tribe.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ruvkun, G. The perfect storm of tiny RNAs. Nat Med 14, 1041–1045 (2008). https://doi.org/10.1038/nm1008-1041
Issue Date:
DOI: https://doi.org/10.1038/nm1008-1041
This article is cited by
-
MiR-489 suppresses tumor growth and invasion by targeting HDAC7 in colorectal cancer
Clinical and Translational Oncology (2018)
-
microRNAs regulate nitric oxide release from endothelial cells by targeting NOS3
Journal of Thrombosis and Thrombolysis (2018)
-
Plasma-specific microRNA response induced by acute exposure to aristolochic acid I in rats
Archives of Toxicology (2017)
-
A panel of microRNAs as a new biomarkers for the detection of deep vein thrombosis
Journal of Thrombosis and Thrombolysis (2015)
-
MicroRNAs—mediators of myometrial contractility during pregnancy and labour
Nature Reviews Endocrinology (2013)