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.
Subscribe

Logo for

Science 308 (5725): 1164-1167

Copyright © 2005 by the American Association for the Advancement of Science

Functional Genomic Analysis of RNA Interference in C. elegans

John K. Kim,1,2* Harrison W. Gabel,1,2* Ravi S. Kamath,1,2*{dagger} Muneesh Tewari,2,3,4,5 Amy Pasquinelli,1,2{ddagger} Jean-François Rual,2,3 Scott Kennedy,1,2§ Michael Dybbs,1,2 Nicolas Bertin,2,3,5 Joshua M. Kaplan,1,2 Marc Vidal,2,3,5 Gary Ruvkun1,2||

Abstract: RNA interference (RNAi) of target genes is triggered by double-stranded RNAs (dsRNAs) processed by conserved nucleases and accessory factors. To identify the genetic components required for RNAi, we performed a genome-wide screen using an engineered RNAi sensor strain of Caenorhabditis elegans. The RNAi screen identified 90 genes. These included Piwi/PAZ proteins, DEAH helicases, RNA binding/processing factors, chromatin-associated factors, DNA recombination proteins, nuclear import/export factors, and 11 known components of the RNAi machinery. We demonstrate that some of these genes are also required for germline and somatic transgene silencing. Moreover, the physical interactions among these potential RNAi factors suggest links to other RNA-dependent gene regulatory pathways.

1 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
2 Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
3 Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
4 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
5 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

* These authors contributed equally to this work.

{dagger} Present address: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.

{ddagger} Present address: Molecular Biology Section, Division of Biology, University of California, San Diego, La Jolla, CA 92093–0349, USA.

§ §Present address: Department of Pharmacology, University of Wisconsin, Madison, WI 53706, USA.

|| To whom correspondence should be addressed. E-mail: ruvkun{at}molbio.mgh.harvard.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Nuclear Argonaute NRDE-3 Contributes to Transitive RNAi in Caenorhabditis elegans.
J. J. Zhuang, S. A. Banse, and C. P. Hunter (2013)
Genetics 194, 117-131
   Abstract »    Full Text »    PDF »
The Draft Genome and Transcriptome of Panagrellus redivivus Are Shaped by the Harsh Demands of a Free-Living Lifestyle.
J. Srinivasan, A. R. Dillman, M. G. Macchietto, L. Heikkinen, M. Lakso, K. M. Fracchia, I. Antoshechkin, A. Mortazavi, G. Wong, and P. W. Sternberg (2013)
Genetics 193, 1279-1295
   Abstract »    Full Text »    PDF »
CloudMap: A Cloud-Based Pipeline for Analysis of Mutant Genome Sequences.
G. Minevich, D. S. Park, D. Blankenberg, R. J. Poole, and O. Hobert (2012)
Genetics 192, 1249-1269
   Abstract »    Full Text »    PDF »
A Network of Genes Antagonistic to the LIN-35 Retinoblastoma Protein of Caenorhabditis elegans.
S. R. G. Polley and D. S. Fay (2012)
Genetics 191, 1367-1380
   Abstract »    Full Text »    PDF »
MUT-16 promotes formation of perinuclear Mutator foci required for RNA silencing in the C. elegans germline.
C. M. Phillips, T. A. Montgomery, P. C. Breen, and G. Ruvkun (2012)
Genes & Dev. 26, 1433-1444
   Abstract »    Full Text »    PDF »
MORC Family ATPases Required for Heterochromatin Condensation and Gene Silencing.
G. Moissiard, S. J. Cokus, J. Cary, S. Feng, A. C. Billi, H. Stroud, D. Husmann, Y. Zhan, B. R. Lajoie, R. P. McCord, et al. (2012)
Science 336, 1448-1451
   Abstract »    Full Text »    PDF »
Closed-form density-based framework for automatic detection of cellular morphology changes.
T. Duong, B. Goud, and K. Schauer (2012)
PNAS 109, 8382-8387
   Abstract »    Full Text »    PDF »
The RDE-10/RDE-11 complex triggers RNAi-induced mRNA degradation by association with target mRNA in C. elegans.
H. Yang, Y. Zhang, J. Vallandingham, H. Li, L. Florens, and H. Y. Mak (2012)
Genes & Dev. 26, 846-856
   Abstract »    Full Text »    PDF »
mut-16 and other mutator class genes modulate 22G and 26G siRNA pathways in Caenorhabditis elegans.
C. Zhang, T. A. Montgomery, H. W. Gabel, S. E. J. Fischer, C. M. Phillips, N. Fahlgren, C. M. Sullivan, J. C. Carrington, and G. Ruvkun (2011)
PNAS 108, 1201-1208
   Abstract »    Full Text »    PDF »
Germ Cell Genes and Cancer.
X. Wu and G. Ruvkun (2010)
Science 330, 1761-1762
   Abstract »    Full Text »    PDF »
Profiling Sex-Specific piRNAs in Zebrafish.
X. Zhou, Z. Zuo, F. Zhou, W. Zhao, Y. Sakaguchi, T. Suzuki, T. Suzuki, H. Cheng, and R. Zhou (2010)
Genetics 186, 1175-1185
   Abstract »    Full Text »    PDF »
Predicting genetic modifier loci using functional gene networks.
I. Lee, B. Lehner, T. Vavouri, J. Shin, A. G. Fraser, and E. M. Marcotte (2010)
Genome Res. 20, 1143-1153
   Abstract »    Full Text »    PDF »
In vivo RNAi: Today and Tomorrow.
N. Perrimon, J.-Q. Ni, and L. Perkins (2010)
Cold Spring Harb Perspect Biol 2, a003640
   Abstract »    Full Text »    PDF »
Distinct RNA-dependent RNA polymerases are required for RNAi triggered by double-stranded RNA versus truncated transgenes in Paramecium tetraurelia.
S. Marker, A. Le Mouel, E. Meyer, and M. Simon (2010)
Nucleic Acids Res. 38, 4092-4107
   Abstract »    Full Text »    PDF »
The RNA Binding Protein Tudor-SN Is Essential for Stress Tolerance and Stabilizes Levels of Stress-Responsive mRNAs Encoding Secreted Proteins in Arabidopsis.
N. F. dit Frey, P. Muller, F. Jammes, D. Kizis, J. Leung, C. Perrot-Rechenmann, and M. W. Bianchi (2010)
PLANT CELL 22, 1575-1591
   Abstract »    Full Text »    PDF »
The spatial dynamics of tissue-specific promoters during C. elegans development.
P. Meister, B. D. Towbin, B. L. Pike, A. Ponti, and S. M. Gasser (2010)
Genes & Dev. 24, 766-782
   Abstract »    Full Text »    PDF »
Targeted 3' Processing of Antisense Transcripts Triggers Arabidopsis FLC Chromatin Silencing.
F. Liu, S. Marquardt, C. Lister, S. Swiezewski, and C. Dean (2010)
Science 327, 94-97
   Abstract »    Full Text »    PDF »
Suppression of RNA silencing by Flock house virus B2 protein is mediated through its interaction with the PAZ domain of Dicer.
G. Singh, S. Popli, Y. Hari, P. Malhotra, S. Mukherjee, and R. K. Bhatnagar (2009)
FASEB J 23, 1845-1857
   Abstract »    Full Text »    PDF »
A genetic screen for components of the mammalian RNA interference pathway in Bloom-deficient mouse embryonic stem cells.
M. I. Trombly, H. Su, and X. Wang (2009)
Nucleic Acids Res. 37, e34
   Abstract »    Full Text »    PDF »
RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans.
A. Grishok, S. Hoersch, and P. A. Sharp (2008)
PNAS 105, 20386-20391
   Abstract »    Full Text »    PDF »
Splicing Factors Facilitate RNAi-Directed Silencing in Fission Yeast.
E. H. Bayne, M. Portoso, A. Kagansky, I. C. Kos-Braun, T. Urano, K. Ekwall, F. Alves, J. Rappsilber, and R. C. Allshire (2008)
Science 322, 602-606
   Abstract »    Full Text »    PDF »
ADBP-1 Regulates an ADAR RNA-Editing Enzyme to Antagonize RNA-Interference-Mediated Gene Silencing in Caenorhabditis elegans.
H. Ohta, M. Fujiwara, Y. Ohshima, and T. Ishihara (2008)
Genetics 180, 785-796
   Abstract »    Full Text »    PDF »
Studying gene function in Caenorhabditis elegans using RNA-mediated interference.
E. M. Maine (2008)
Briefings in Functional Genomics 7, 184-194
   Abstract »    Full Text »    PDF »
DEPS-1 promotes P-granule assembly and RNA interference in C. elegans germ cells.
C. A. Spike, J. Bader, V. Reinke, and S. Strome (2008)
Development 135, 983-993
   Abstract »    Full Text »    PDF »
The Caenorhabditis elegans ekl (Enhancer of ksr-1 Lethality) Genes Include Putative Components of a Germline Small RNA Pathway.
C. E. Rocheleau, K. Cullison, K. Huang, Y. Bernstein, A. C. Spilker, and M. V. Sundaram (2008)
Genetics 178, 1431-1443
   Abstract »    Full Text »    PDF »
Median Absolute Deviation to Improve Hit Selection for Genome-Scale RNAi Screens.
N. Chung, X. D. Zhang, A. Kreamer, L. Locco, P.-F. Kuan, S. Bartz, P. S. Linsley, M. Ferrer, and B. Strulovici (2008)
J Biomol Screen 13, 149-158
   Abstract »    PDF »
Caenorhabditis elegans ABCRNAi Transporters Interact Genetically With rde-2 and mut-7.
P. Sundaram, W. Han, N. Cohen, B. Echalier, J. Albin, and L. Timmons (2008)
Genetics 178, 801-814
   Abstract »    Full Text »    PDF »
Current progress in network research: toward reference networks for key model organisms.
B. S. Srinivasan, N. H. Shah, J. A. Flannick, E. Abeliuk, A. F. Novak, and S. Batzoglou (2007)
Brief Bioinform 8, 318-332
   Abstract »    Full Text »    PDF »
A Cluster of Disease Resistance Genes in Arabidopsis Is Coordinately Regulated by Transcriptional Activation and RNA Silencing.
H. Yi and E. J. Richards (2007)
PLANT CELL 19, 2929-2939
   Abstract »    Full Text »    PDF »
Oryza sativa Dicer-like4 Reveals a Key Role for Small Interfering RNA Silencing in Plant Development.
B. Liu, Z. Chen, X. Song, C. Liu, X. Cui, X. Zhao, J. Fang, W. Xu, H. Zhang, X. Wang, et al. (2007)
PLANT CELL 19, 2705-2718
   Abstract »    Full Text »    PDF »
Genome-wide functional analysis of human cell-cycle regulators.
M. Mukherji, R. Bell, L. Supekova, Y. Wang, A. P. Orth, S. Batalov, L. Miraglia, D. Huesken, J. Lange, C. Martin, et al. (2006)
PNAS 103, 14819-14824
   Abstract »    Full Text »    PDF »
A genomewide screen for components of the RNAi pathway in Drosophila cultured cells.
S. Dorner, L. Lum, M. Kim, R. Paro, P. A. Beachy, and R. Green (2006)
PNAS 103, 11880-11885
   Abstract »    Full Text »    PDF »
ATP-binding Cassette Transporters Are Required for Efficient RNA Interference in Caenorhabditis elegans.
P. Sundaram, B. Echalier, W. Han, D. Hull, and L. Timmons (2006)
Mol. Biol. Cell 17, 3678-3688
   Abstract »    Full Text »    PDF »
Interacting endogenous and exogenous RNAi pathways in Caenorhabditis elegans.
R. C. LEE, C. M. HAMMELL, and V. AMBROS (2006)
RNA 12, 589-597
   Abstract »    Full Text »    PDF »
Differential contributions of Caenorhabditis elegans histone deacetylases to huntingtin polyglutamine toxicity..
E. A. Bates, M. Victor, A. K. Jones, Y. Shi, and A. C. Hart (2006)
J. Neurosci. 26, 2830-2838
   Abstract »    Full Text »    PDF »
Functional mapping of disease susceptibility loci using cell biology..
P. A. Antinozzi, A. Garcia-Diaz, C. Hu, and J. E. Rothman (2006)
PNAS 103, 3698-3703
   Abstract »    Full Text »    PDF »
URI-1 is required for DNA stability in C. elegans.
C. T. Parusel, E. A. Kritikou, M. O. Hengartner, W. Krek, and M. Gotta (2006)
Development 133, 621-629
   Abstract »    Full Text »    PDF »
gon-14 Functions With Class B and Class C Synthetic Multivulva Genes to Control Larval Growth in Caenorhabditis elegans.
M. A. Chesney, A. R. Kidd III, and J. Kimble (2006)
Genetics 172, 915-928
   Abstract »    Full Text »    PDF »
An antiviral role for the RNA interference machinery in Caenorhabditis elegans.
D. H. Schott, D. K. Cureton, S. P. Whelan, and C. P. Hunter (2005)
PNAS 102, 18420-18424
   Abstract »    Full Text »    PDF »
A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing.
J. REHWINKEL, I. BEHM-ANSMANT, D. GATFIELD, and E. IZAURRALDE (2005)
RNA 11, 1640-1647
   Abstract »    Full Text »    PDF »
Nonsense-mediated mRNA decay factors act in concert to regulate common mRNA targets.
J. REHWINKEL, I. LETUNIC, J. RAES, P. BORK, and E. IZAURRALDE (2005)
RNA 11, 1530-1544
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882