Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 26 October 2001:
Vol. 294. no. 5543, pp. 858 - 862
DOI: 10.1126/science.1065062
Prev | Table of Contents | Next

Reports

An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans

Nelson C. Lau, Lee P. Lim, Earl G. Weinstein, David P. Bartel*

Two small temporal RNAs (stRNAs), lin-4 and let-7, control developmental timing in Caenorhabditis elegans. We find that these two regulatory RNAs are members of a large class of 21- to 24-nucleotide noncoding RNAs, called microRNAs (miRNAs). We report on 55 previously unknown miRNAs in C. elegans. The miRNAs have diverse expression patterns during development: a let-7 paralog is temporally coexpressed with let-7; miRNAs encoded in a single genomic cluster are coexpressed during embryogenesis; and still other miRNAs are expressed constitutively throughout development. Potential orthologs of several of these miRNA genes were identified in Drosophila and human genomes. The abundance of these tiny RNAs, their expression patterns, and their evolutionary conservation imply that, as a class, miRNAs have broad regulatory functions in animals.

Whitehead Institute for Biomedical Research, and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.
*   To whom correspondence should be addressed. E-mail: dbartel{at}wi.mit.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Lost in translation: an assessment and perspective for computational microRNA target identification.
P. Alexiou, M. Maragkakis, G. L. Papadopoulos, M. Reczko, and A. G. Hatzigeorgiou (2009)
Bioinformatics 25, 3049-3055
   Abstract »    Full Text »    PDF »
MicroRNAs and Beyond: The Heart Reveals Its Treasures.
B. Schroen and S. Heymans (2009)
Hypertension 54, 1189-1194
   Full Text »    PDF »
A novel class of small RNAs: tRNA-derived RNA fragments (tRFs).
Y. S. Lee, Y. Shibata, A. Malhotra, and A. Dutta (2009)
Genes & Dev. 23, 2639-2649
   Abstract »    Full Text »    PDF »
Deciphering the diversity of small RNAs in plants: the long and short of it.
F. Schwach, S. Moxon, V. Moulton, and T. Dalmay (2009)
Brief Funct Genomic Proteomic 8, 472-481
   Abstract »    Full Text »    PDF »
The 5'-end heterogeneity of adenovirus virus-associated RNAI contributes to the asymmetric guide strand incorporation into the RNA-induced silencing complex.
N. Xu, S. Gkountela, K. Saeed, and G. Akusjarvi (2009)
Nucleic Acids Res. 37, 6950-6959
   Abstract »    Full Text »    PDF »
Repertoire and evolution of miRNA genes in four divergent nematode species.
E. de Wit, S. E.V. Linsen, E. Cuppen, and E. Berezikov (2009)
Genome Res. 19, 2064-2074
   Abstract »    Full Text »    PDF »
RNAi in Budding Yeast.
I. A. Drinnenberg, D. E. Weinberg, K. T. Xie, J. P. Mower, K. H. Wolfe, G. R. Fink, and D. P. Bartel (2009)
Science 326, 544-550
   Abstract »    Full Text »    PDF »
Sequence-non-specific effects of RNA interference triggers and microRNA regulators.
M. Olejniczak, P. Galka, and W. J. Krzyzosiak (2009)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
Analysis of Human Alphaherpesvirus MicroRNA Expression in Latently Infected Human Trigeminal Ganglia.
J. L. Umbach, M. A. Nagel, R. J. Cohrs, D. H. Gilden, and B. R. Cullen (2009)
J. Virol. 83, 10677-10683
   Abstract »    Full Text »    PDF »
miRNA deregulation by epigenetic silencing disrupts suppression of the oncogene PLAG1 in chronic lymphocytic leukemia.
C. P. Pallasch, M. Patz, Y. J. Park, S. Hagist, D. Eggle, R. Claus, S. Debey-Pascher, A. Schulz, L. P. Frenzel, J. Claasen, et al. (2009)
Blood 114, 3255-3264
   Abstract »    Full Text »    PDF »
Messenger RNA processing in Methanocaldococcus (Methanococcus) jannaschii.
J. Zhang and G. J. Olsen (2009)
RNA 15, 1909-1916
   Abstract »    Full Text »    PDF »
Pyrosequencing of small non-coding RNAs in HIV-1 infected cells: evidence for the processing of a viral-cellular double-stranded RNA hybrid.
M. L. Yeung, Y. Bennasser, K. Watashi, S.-Y. Le, L. Houzet, and K.-T. Jeang (2009)
Nucleic Acids Res. 37, 6575-6586
   Abstract »    Full Text »    PDF »
Epigenetics of endometriosis.
S.-W. Guo (2009)
Mol. Hum. Reprod. 15, 587-607
   Abstract »    Full Text »    PDF »
Abundant and dynamically expressed miRNAs, piRNAs, and other small RNAs in the vertebrate Xenopus tropicalis.
J. Armisen, M. J. Gilchrist, A. Wilczynska, N. Standart, and E. A. Miska (2009)
Genome Res. 19, 1766-1775
   Abstract »    Full Text »    PDF »
Chromatin poises miRNA- and protein-coding genes for expression.
A. Barski, R. Jothi, S. Cuddapah, K. Cui, T.-Y. Roh, D. E. Schones, and K. Zhao (2009)
Genome Res. 19, 1742-1751
   Abstract »    Full Text »    PDF »
Human Villous Trophoblasts Express and Secrete Placenta-Specific MicroRNAs into Maternal Circulation via Exosomes.
S.-S. Luo, O. Ishibashi, G. Ishikawa, T. Ishikawa, A. Katayama, T. Mishima, T. Takizawa, T. Shigihara, T. Goto, A. Izumi, et al. (2009)
Biol Reprod 81, 717-729
   Abstract »    Full Text »    PDF »
The role of microRNAs in endometriosis and associated reproductive conditions.
E. M. C. Ohlsson Teague, C. G. Print, and M. L. Hull (2009)
Hum. Reprod. Update
   Abstract »    Full Text »    PDF »
Expression profiling of microRNAs by deep sequencing.
C. J. Creighton, J. G. Reid, and P. H. Gunaratne (2009)
Brief Bioinform 10, 490-497
   Abstract »    Full Text »    PDF »
Profiling and Discovery of Novel miRNAs from Formalin-Fixed, Paraffin-Embedded Melanoma and Nodal Specimens.
Z. Ma, W.-O. Lui, A. Fire, and S. S. Dadras (2009)
J. Mol. Diagn. 11, 420-429
   Abstract »    Full Text »    PDF »
Salivary microRNA: Discovery, Characterization, and Clinical Utility for Oral Cancer Detection.
N. J. Park, H. Zhou, D. Elashoff, B. S. Henson, D. A. Kastratovic, E. Abemayor, and D. T. Wong (2009)
Clin. Cancer Res. 15, 5473-5477
   Abstract »    Full Text »    PDF »
Telomeric RNAs Mark Sex Chromosomes in Stem Cells.
L.-F. Zhang, Y. Ogawa, J. Y. Ahn, S. H. Namekawa, S. S. Silva, and J. T. Lee (2009)
Genetics 182, 685-698
   Abstract »    Full Text »    PDF »
Evolution under canalization and the dual roles of microRNAs--A hypothesis.
C.-I Wu, Y. Shen, and T. Tang (2009)
Genome Res. 19, 734-743
   Abstract »    Full Text »    PDF »
Meta-analysis of small RNA-sequencing errors reveals ubiquitous post-transcriptional RNA modifications.
H. A. Ebhardt, H. H. Tsang, D. C. Dai, Y. Liu, B. Bostan, and R. P. Fahlman (2009)
Nucleic Acids Res. 37, 2461-2470
   Abstract »    Full Text »    PDF »
Current tools for the identification of miRNA genes and their targets.
N. D. Mendes, A. T. Freitas, and M.-F. Sagot (2009)
Nucleic Acids Res. 37, 2419-2433
   Abstract »    Full Text »    PDF »
Evolutionary Origin and Genomic Organization of Micro-RNA Genes in Immunoglobulin Lambda Variable Region Gene Family.
S. Das (2009)
Mol. Biol. Evol. 26, 1179-1189
   Abstract »    Full Text »    PDF »
The Phloem-Delivered RNA Pool Contains Small Noncoding RNAs and Interferes with Translation.
S. Zhang, L. Sun, and F. Kragler (2009)
Plant Physiology 150, 378-387
   Abstract »    Full Text »    PDF »
MicroRNAs: Regulating a Change of Heart.
K. G. Barringhaus and P. D. Zamore (2009)
Circulation 119, 2217-2224
   Full Text »    PDF »
Experimental discovery of sRNAs in Vibrio cholerae by direct cloning, 5S/tRNA depletion and parallel sequencing.
J. M. Liu, J. Livny, M. S. Lawrence, M. D. Kimball, M. K. Waldor, and A. Camilli (2009)
Nucleic Acids Res. 37, e46
   Abstract »    Full Text »    PDF »
A Functional Genetic Variant in microRNA-196a2 Is Associated with Increased Susceptibility of Lung Cancer in Chinese.
T. Tian, Y. Shu, J. Chen, Z. Hu, L. Xu, G. Jin, J. Liang, P. Liu, X. Zhou, R. Miao, et al. (2009)
Cancer Epidemiol. Biomarkers Prev. 18, 1183-1187
   Abstract »    Full Text »    PDF »
Congruent Evolution of Genetic and Environmental Robustness in Micro-RNA.
G. J. Szollosi and I. Derenyi (2009)
Mol. Biol. Evol. 26, 867-874
   Abstract »    Full Text »    PDF »
MicroRNA: Mechanism of gene regulation and application to livestock.
T. G. McDaneld (2009)
J Anim Sci 87, E21-E28
   Abstract »    Full Text »    PDF »
Cellular versus viral microRNAs in host-virus interaction.
Z. Ghosh, B. Mallick, and J. Chakrabarti (2009)
Nucleic Acids Res. 37, 1035-1048
   Abstract »    Full Text »    PDF »
Impaired Micro-RNA Pathways Diminish Osteoclast Differentiation and Function.
T. Sugatani and K. A. Hruska (2009)
J. Biol. Chem. 284, 4667-4678
   Abstract »    Full Text »    PDF »
MicroRNA-like off-target transcript regulation by siRNAs is species specific.
J. Burchard, A. L. Jackson, V. Malkov, R. H.V. Needham, Y. Tan, S. R. Bartz, H. Dai, A. B. Sachs, and P. S. Linsley (2009)
RNA 15, 308-315
   Abstract »    Full Text »    PDF »
A regulatory interplay between miR-27a and Runx1 during megakaryopoiesis.
O. Ben-Ami, N. Pencovich, J. Lotem, D. Levanon, and Y. Groner (2009)
PNAS 106, 238-243
   Abstract »    Full Text »    PDF »
Hepatitis B virus (HBV)-specific short hairpin RNA is capable of reducing the formation of HBV covalently closed circular (CCC) DNA but has no effect on established CCC DNA in vitro.
J. L. Starkey, E. F. Chiari, and H. C. Isom (2009)
J. Gen. Virol. 90, 115-126
   Abstract »    Full Text »    PDF »
Integrating the MicroRNome into the Study of Lung Disease.
S. P. Nana-Sinkam, M. G. Hunter, G. J. Nuovo, T. D. Schmittgen, R. Gelinas, D. Galas, and C. B. Marsh (2009)
Am. J. Respir. Crit. Care Med. 179, 4-10
   Abstract »    Full Text »    PDF »
The database of experimentally supported targets: a functional update of TarBase.
G. L. Papadopoulos, M. Reczko, V. A. Simossis, P. Sethupathy, and A. G. Hatzigeorgiou (2009)
Nucleic Acids Res. 37, D155-D158
   Abstract »    Full Text »    PDF »
MicroRNA in Cancer Prognosis.
F. J. Slack and J. B. Weidhaas (2008)
N. Engl. J. Med. 359, 2720-2722
   Full Text »    PDF »
Prokaryotic silencing (psi)RNAs in Pyrococcus furiosus.
C. Hale, K. Kleppe, R. M. Terns, and M. P. Terns (2008)
RNA 14, 2572-2579
   Abstract »    Full Text »    PDF »
MicroRNA (miRNA) cloning analysis reveals sex differences in miRNA expression profiles between adult mouse testis and ovary.
T. Mishima, T. Takizawa, S.-S. Luo, O. Ishibashi, Y. Kawahigashi, Y. Mizuguchi, T. Ishikawa, M. Mori, T. Kanda, T. Goto, et al. (2008)
Reproduction 136, 811-822
   Abstract »    Full Text »    PDF »
Genome-scale spatiotemporal analysis of Caenorhabditis elegans microRNA promoter activity.
N. J. Martinez, M. C. Ow, J. S. Reece-Hoyes, M. I. Barrasa, V. R. Ambros, and A. J.M. Walhout (2008)
Genome Res. 18, 2005-2015
   Abstract »    Full Text »    PDF »
Adding fuel to fire: microRNAs as a new class of mediators of inflammation.
F J Sheedy and L A J O'Neill (2008)
Ann Rheum Dis 67, iii50-iii55
   Abstract »    Full Text »    PDF »
Chromatin structure analyses identify miRNA promoters.
F. Ozsolak, L. L. Poling, Z. Wang, H. Liu, X. S. Liu, R. G. Roeder, X. Zhang, J. S. Song, and D. E. Fisher (2008)
Genes & Dev. 22, 3172-3183
   Abstract »    Full Text »    PDF »
A novel biochemical method to identify target genes of individual microRNAs: Identification of a new Caenorhabditis elegans let-7 target.
Y. Andachi (2008)
RNA 14, 2440-2451
   Abstract »    Full Text »    PDF »
Mouse let-7 miRNA populations exhibit RNA editing that is constrained in the 5'-seed/ cleavage/anchor regions and stabilize predicted mmu-let-7a:mRNA duplexes.
J. G. Reid, A. K. Nagaraja, F. C. Lynn, R. B. Drabek, D. M. Muzny, C. A. Shaw, M. K. Weiss, A. O. Naghavi, M. Khan, H. Zhu, et al. (2008)
Genome Res. 18, 1571-1581
   Abstract »    Full Text »    PDF »
A starvation-induced noncoding RNA modulates expression of Dicer-regulated genes.
S. Hellwig and B. L. Bass (2008)
PNAS 105, 12897-12902
   Abstract »    Full Text »    PDF »
An intronic microRNA silences genes that are functionally antagonistic to its host gene.
S. Barik (2008)
Nucleic Acids Res. 36, 5232-5241
   Abstract »    Full Text »    PDF »
The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease.
M. M.W. Chong, J. P. Rasmussen, A. Y. Rudensky, and D. R. Littman (2008)
J. Exp. Med. 205, 2005-2017
   Abstract »    Full Text »    PDF »
The Emergent Role of MicroRNAs in Molecular Diagnostics of Cancer.
W. Tam (2008)
J. Mol. Diagn. 10, 411-414
   Abstract »    Full Text »    PDF »
MicroRNA Expression and Regulation in Mouse Uterus during Embryo Implantation.
S.-J. Hu, G. Ren, J.-L. Liu, Z.-A. Zhao, Y.-S. Yu, R.-W. Su, X.-H. Ma, H. Ni, W. Lei, and Z.-M. Yang (2008)
J. Biol. Chem. 283, 23473-23484
   Abstract »    Full Text »    PDF »
Highly sensitive and specific microRNA expression profiling using BeadArray technology.
J. Chen, J. Lozach, E. W. Garcia, B. Barnes, S. Luo, I. Mikoulitch, L. Zhou, G. Schroth, and J.-B. Fan (2008)
Nucleic Acids Res. 36, e87
   Abstract »    Full Text »    PDF »
Functional genomic, computational and proteomic analysis of C. elegans microRNAs.
N. J. Lehrbach and E. A. Miska (2008)
Brief Funct Genomic Proteomic
   Abstract »    Full Text »    PDF »
miRNAs: Effectors of Environmental Influences on Gene Expression and Disease.
A. Hudder and R. F. Novak (2008)
Toxicol. Sci. 103, 228-240
   Abstract »    Full Text »    PDF »
Adaptive Evolution of Newly Emerged Micro-RNA Genes in Drosophila.
J. Lu, Y. Fu, S. Kumar, Y. Shen, K. Zeng, A. Xu, R. Carthew, and C.-I Wu (2008)
Mol. Biol. Evol. 25, 929-938
   Abstract »    Full Text »    PDF »
MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins.
S. Sengupta, J. A. den Boon, I-H. Chen, M. A. Newton, S. A. Stanhope, Y.-J. Cheng, C.-J. Chen, A. Hildesheim, B. Sugden, and P. Ahlquist (2008)
PNAS 105, 5874-5878
   Abstract »    Full Text »    PDF »
Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: Implications for the therapeutic development of RNAi.
J. L. McBride, R. L. Boudreau, S. Q. Harper, P. D. Staber, A. M. Monteys, I. Martins, B. L. Gilmore, H. Burstein, R. W. Peluso, B. Polisky, et al. (2008)
PNAS 105, 5868-5873
   Abstract »    Full Text »    PDF »
Detection and Characterization of Placental MicroRNAs in Maternal Plasma.
S. S.C. Chim, T. K.F. Shing, E. C.W. Hung, T.-y. Leung, T.-k. Lau, R. W.K. Chiu, and Y.M. Dennis Lo (2008)
Clin. Chem. 54, 482-490
   Abstract »    Full Text »    PDF »
MicroRNA expression profiling in classic Hodgkin lymphoma.
A. Navarro, A. Gaya, A. Martinez, A. Urbano-Ispizua, A. Pons, O. Balague, B. Gel, P. Abrisqueta, A. Lopez-Guillermo, R. Artells, et al. (2008)
Blood 111, 2825-2832
   Abstract »    Full Text »    PDF »
Developmentally regulated cleavage of tRNAs in the bacterium Streptomyces coelicolor.
H. J. Haiser, F. V. Karginov, G. J. Hannon, and M. A. Elliot (2008)
Nucleic Acids Res. 36, 732-741
   Abstract »    Full Text »    PDF »
In Vitro and In Silico Annotation of Conserved and Nonconserved MicroRNAs in the Genome of the Marsupial Monodelphis domestica.
E. J. Devor and P. B. Samollow (2008)
J. Hered.
   Full Text »    PDF »
Strand-specific 5'-O-methylation of siRNA duplexes controls guide strand selection and targeting specificity.
P. Y. Chen, L. Weinmann, D. Gaidatzis, Y. Pei, M. Zavolan, T. Tuschl, and G. Meister (2008)
RNA 14, 263-274
   Abstract »    Full Text »    PDF »
Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells.
L. B. Frankel, N. R. Christoffersen, A. Jacobsen, M. Lindow, A. Krogh, and A. H. Lund (2008)
J. Biol. Chem. 283, 1026-1033
   Abstract »    Full Text »    PDF »
Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors.
E. J. Lee, M. Baek, Y. Gusev, D. J. Brackett, G. J. Nuovo, and T. D. Schmittgen (2008)
RNA 14, 35-42
   Abstract »    Full Text »    PDF »
Functionally distinct regulatory RNAs generated by bidirectional transcription and processing of microRNA loci.
D. M. Tyler, K. Okamura, W.-J. Chung, J. W. Hagen, E. Berezikov, G. J. Hannon, and E. C. Lai (2008)
Genes & Dev. 22, 26-36
   Abstract »    Full Text »    PDF »
Xenopus microRNA genes are predominantly located within introns and are differentially expressed in adult frog tissues via post-transcriptional regulation.
G.-Q. Tang and E. S. Maxwell (2008)
Genome Res. 18, 104-112
   Abstract »    Full Text »    PDF »
Discrete Clusters of Virus-Encoded MicroRNAs Are Associated with Complementary Strands of the Genome and the 7.2-Kilobase Stable Intron in Murine Cytomegalovirus.
A. H. Buck, J. Santoyo-Lopez, K. A. Robertson, D. S. Kumar, M. Reczko, and P. Ghazal (2007)
J. Virol. 81, 13761-13770
   Abstract »    Full Text »    PDF »
Mouse Cytomegalovirus MicroRNAs Dominate the Cellular Small RNA Profile during Lytic Infection and Show Features of Posttranscriptional Regulation.
L. Dolken, J. Perot, V. Cognat, A. Alioua, M. John, J. Soutschek, Z. Ruzsics, U. Koszinowski, O. Voinnet, and S. Pfeffer (2007)
J. Virol. 81, 13771-13782
   Abstract »    Full Text »    PDF »
Emerging Role of MicroRNAs in Cardiovascular Biology.
M. V.G. Latronico, D. Catalucci, and G. Condorelli (2007)
Circ. Res. 101, 1225-1236
   Abstract »    Full Text »    PDF »
Cloning and expression profiling of small RNAs expressed in the mouse ovary.
S. Ro, R. Song, C. Park, H. Zheng, K. M. Sanders, and W. Yan (2007)
RNA 13, 2366-2380
   Abstract »    Full Text »    PDF »
MicroRNAs as Potential Agents to Alter Resistance to Cytotoxic Anticancer Therapy.
J. B. Weidhaas, I. Babar, S. M. Nallur, P. Trang, S. Roush, M. Boehm, E. Gillespie, and F. J. Slack (2007)
Cancer Res. 67, 11111-11116
   Abstract »    Full Text »    PDF »
Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomes.
A. Stark, P. Kheradpour, L. Parts, J. Brennecke, E. Hodges, G. J. Hannon, and M. Kellis (2007)
Genome Res. 17, 1865-1879
   Abstract »    Full Text »    PDF »
Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAs.
J. G. Ruby, A. Stark, W. K. Johnston, M. Kellis, D. P. Bartel, and E. C. Lai (2007)
Genome Res. 17, 1850-1864
   Abstract »    Full Text »    PDF »
MicroRNA Expression Is Required for Pancreatic Islet Cell Genesis in the Mouse.
F. C. Lynn, P. Skewes-Cox, Y. Kosaka, M. T. McManus, B. D. Harfe, and M. S. German (2007)
Diabetes 56, 2938-2945
   Abstract »    Full Text »    PDF »
The small RNA repertoire of Dictyostelium discoideum and its regulation by components of the RNAi pathway.
A. Hinas, J. Reimegard, E. G. H. Wagner, W. Nellen, V. R. Ambros, and F. Soderbom (2007)
Nucleic Acids Res. 35, 6714-6726
   Abstract »    Full Text »    PDF »
Analysis of the Interaction of Primate Retroviruses with the Human RNA Interference Machinery.
J. Lin and B. R. Cullen (2007)
J. Virol. 81, 12218-12226
   Abstract »    Full Text »    PDF »
A practical guide to the art of RNA gene prediction.
I. M. Meyer (2007)
Brief Bioinform 8, 396-414
   Abstract »    Full Text »    PDF »
A pyrosequencing-tailored nucleotide barcode design unveils opportunities for large-scale sample multiplexing.
P. Parameswaran, R. Jalili, L. Tao, S. Shokralla, B. Gharizadeh, M. Ronaghi, and A. Z. Fire (2007)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)