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.

Published Online June 29, 2006
Science DOI: 10.1126/science.1129333

Research Articles

Submitted on May 1, 2006
Accepted on June 20, 2006

A Distinct Small RNA Pathway Silences Selfish Genetic Elements in the Germline

Vasily V. Vagin 1, Alla Sigova 2, Chengjian Li 2, Hervé Seitz 2, Vladimir Gvozdev 3, Phillip D. Zamore 2*

1 Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Animal Molecular Genetics, Institute of Molecular Genetics, Moscow 123182, Russia.
2 Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
3 Department of Animal Molecular Genetics, Institute of Molecular Genetics, Moscow 123182, Russia.

* To whom correspondence should be addressed.
Phillip D. Zamore , E-mail: phillip.zamore{at}umassmed.edu

In the Drosophila germline, repeat-associated small interfering RNAs (rasiRNAs) ensure genomic stability by silencing endogenous selfish genetic elements such as retrotransposons and repetitive sequences. While small interfering RNAs (siRNAs) derive from both the sense and antisense strands of their double-stranded RNA precursors, rasiRNAs arise mainly from the antisense strand. rasiRNA production appears not to require Dicer-1, which makes microRNAs, or Dicer-2, which makes siRNAs, and rasiRNAs lack the 2',3' hydroxy termini characteristic of animal siRNA and miRNA. Unlike siRNAs and miRNAs, rasiRNAs function through the Piwi, rather than the Ago, Argonaute protein subfamily. Our data suggest that rasiRNAs protect the fly germline through a silencing mechanism distinct from both the miRNA and RNAi pathways.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Retrotransposons and non-protein coding RNAs.
T. Mourier and E. Willerslev (2009)
Brief Funct Genomic Proteomic 8, 493-501
   Abstract »    Full Text »    PDF »
Subtraction by addition: domesticated transposases in programmed DNA elimination.
J. A. Motl and D. L. Chalker (2009)
Genes & Dev. 23, 2455-2460
   Abstract »    Full Text »    PDF »
Structural and biochemical insights into 2'-O-methylation at the 3'-terminal nucleotide of RNA by Hen1.
C. Mui Chan, C. Zhou, J. S. Brunzelle, and R. H. Huang (2009)
PNAS 106, 17699-17704
   Abstract »    Full Text »    PDF »
Reconstituting Bacterial RNA Repair and Modification in Vitro.
C. M. Chan, C. Zhou, and R. H. Huang (2009)
Science 326, 247
   Abstract »    Full Text »    PDF »
Abundant primary piRNAs, endo-siRNAs, and microRNAs in a Drosophila ovary cell line.
N. C. Lau, N. Robine, R. Martin, W.-J. Chung, Y. Niki, E. Berezikov, and E. C. Lai (2009)
Genome Res. 19, 1776-1785
   Abstract »    Full Text »    PDF »
Associations between PIWI proteins and TDRD1/MTR-1 are critical for integrated subcellular localization in murine male germ cells.
K. Kojima, S. Kuramochi-Miyagawa, S. Chuma, T. Tanaka, N. Nakatsuji, T. Kimura, and T. Nakano (2009)
Genes Cells 14, 1155-1165
   Abstract »    Full Text »    PDF »
piRNAs mediate posttranscriptional retroelement silencing and localization to pi-bodies in the Drosophila germline.
A. K. Lim, L. Tao, and T. Kai (2009)
J. Cell Biol. 186, 333-342
   Abstract »    Full Text »    PDF »
Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members.
V. V. Vagin, J. Wohlschlegel, J. Qu, Z. Jonsson, X. Huang, S. Chuma, A. Girard, R. Sachidanandam, G. J. Hannon, and A. A. Aravin (2009)
Genes & Dev. 23, 1749-1762
   Abstract »    Full Text »    PDF »
MIWI-independent small RNAs (MSY-RNAs) bind to the RNA-binding protein, MSY2, in male germ cells.
M. Xu, S. Medvedev, J. Yang, and N. B. Hecht (2009)
PNAS 106, 12371-12376
   Abstract »    Full Text »    PDF »
The Bombyx ovary-derived cell line endogenously expresses PIWI/PIWI-interacting RNA complexes.
S. Kawaoka, N. Hayashi, Y. Suzuki, H. Abe, S. Sugano, Y. Tomari, T. Shimada, and S. Katsuma (2009)
RNA 15, 1258-1264
   Abstract »    Full Text »    PDF »
Epigenetic Programming: The Challenge to Species Hybridization.
R. Ishikawa and T. Kinoshita (2009)
Mol Plant 2, 589-599
   Abstract »    Full Text »    PDF »
Peculiarities of piRNA-mediated post-transcriptional silencing of Stellate repeats in testes of Drosophila melanogaster.
R. N. Kotelnikov, M. S. Klenov, Y. M. Rozovsky, L. V. Olenina, M. V. Kibanov, and V. A. Gvozdev (2009)
Nucleic Acids Res. 37, 3254-3263
   Abstract »    Full Text »    PDF »
Small RNA molecules in the regulation of spermatogenesis.
Z. He, M. Kokkinaki, D. Pant, G I. Gallicano, and M. Dym (2009)
Reproduction 137, 901-911
   Abstract »    Full Text »    PDF »
Computational and analytical framework for small RNA profiling by high-throughput sequencing.
N. Fahlgren, C. M. Sullivan, K. D. Kasschau, E. J. Chapman, J. S. Cumbie, T. A. Montgomery, S. D. Gilbert, M. Dasenko, T. W.H. Backman, S. A. Givan, et al. (2009)
RNA 15, 992-1002
   Abstract »    Full Text »    PDF »
Short non-coding RNA biology and neurodegenerative disorders: novel disease targets and therapeutics.
M. S. Weinberg and M. J.A. Wood (2009)
Hum. Mol. Genet. 18, R27-R39
   Abstract »    Full Text »    PDF »
2'-O-methylation stabilizes Piwi-associated small RNAs and ensures DNA elimination in Tetrahymena.
H. M. Kurth and K. Mochizuki (2009)
RNA 15, 675-685
   Abstract »    Full Text »    PDF »
Dicing of viral replication intermediates during silencing of latent Drosophila viruses.
A. Flynt, N. Liu, R. Martin, and E. C. Lai (2009)
PNAS 106, 5270-5275
   Abstract »    Full Text »    PDF »
Shhh! Silencing by microRNA-155.
G. Teng and F. N. Papavasiliou (2009)
Phil Trans R Soc B 364, 631-637
   Abstract »    Full Text »    PDF »
Small RNA Silencing Pathways in Germ and Stem Cells.
A.A. Aravin and G.J. Hannon (2009)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
A Novel Epigenetic Mechanism in Drosophila Somatic Cells Mediated by PIWI and piRNAs.
H. Lin and H. Yin (2009)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
The evolution of RNAi as a defence against viruses and transposable elements.
D. J Obbard, K. H.J Gordon, A. H Buck, and F. M Jiggins (2009)
Phil Trans R Soc B 364, 99-115
   Abstract »    Full Text »    PDF »
rasiRNA pathway controls antisense expression of Drosophila telomeric retrotransposons in the nucleus.
S. Shpiz, D. Kwon, Y. Rozovsky, and A. Kalmykova (2009)
Nucleic Acids Res. 37, 268-278
   Abstract »    Full Text »    PDF »
Epigenetic Regulation of Retrotransposons within the Nucleolus of Drosophila.
D. G. Eickbush, J. Ye, X. Zhang, W. D. Burke, and T. H. Eickbush (2008)
Mol. Cell. Biol. 28, 6452-6461
   Abstract »    Full Text »    PDF »
piRNA-mediated nuclear accumulation of retrotransposon transcripts in the Drosophila female germline.
S. Chambeyron, A. Popkova, G. Payen-Groschene, C. Brun, D. Laouini, A. Pelisson, and A. Bucheton (2008)
PNAS 105, 14964-14969
   Abstract »    Full Text »    PDF »
The DNA/RNA-Binding Protein, Translin, Binds microRNA122a and Increases Its In Vivo Stability.
Z. Yu and N. B. Hecht (2008)
J Androl 29, 572-579
   Abstract »    Full Text »    PDF »
MicroRNA: basic mechanisms and transcriptional regulatory networks for cell fate determination.
F. Fazi and C. Nervi (2008)
Cardiovasc Res 79, 553-561
   Abstract »    Full Text »    PDF »
Cytotype Regulation of P Transposable Elements in Drosophila melanogaster: Repressor Polypeptides or piRNAs?.
P. A. Jensen, J. R. Stuart, M. P. Goodpaster, J. W. Goodman, and M. J. Simmons (2008)
Genetics 179, 1785-1793
   Abstract »    Full Text »    PDF »
Mice Deficient for a Small Cluster of Piwi-Interacting RNAs Implicate Piwi-Interacting RNAs in Transposon Control.
M. Xu, Y. You, P. Hunsicker, T. Hori, C. Small, M. D Griswold, and N. B Hecht (2008)
Biol Reprod 79, 51-57
   Abstract »    Full Text »    PDF »
Organization and transcriptional output of a novel mRNA-like piRNA gene (mpiR) located on mouse chromosome 10.
M. Kim, B. Patel, K. E. Schroeder, A. Raza, and J. Dejong (2008)
RNA 14, 1005-1011
   Abstract »    Full Text »    PDF »
The PIWI proteins SMEDWI-2 and SMEDWI-3 are required for stem cell function and piRNA expression in planarians.
D. Palakodeti, M. Smielewska, Y.-C. Lu, G. W. Yeo, and B. R. Graveley (2008)
RNA 14, 1174-1186
   Abstract »    Full Text »    PDF »
Endogenous siRNAs Derived from Transposons and mRNAs in Drosophila Somatic Cells.
M. Ghildiyal, H. Seitz, M. D. Horwich, C. Li, T. Du, S. Lee, J. Xu, E. L.W. Kittler, M. L. Zapp, Z. Weng, et al. (2008)
Science 320, 1077-1081
   Abstract »    Full Text »    PDF »
Small RNA guides for de novo DNA methylation in mammalian germ cells.
A. A. Aravin and D. Bourc'his (2008)
Genes & Dev. 22, 970-975
   Abstract »    Full Text »    PDF »
The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members.
T. A. Farazi, S. A. Juranek, and T. Tuschl (2008)
Development 135, 1201-1214
   Abstract »    Full Text »    PDF »
A cryptic unstable transcript mediates transcriptional trans-silencing of the Ty1 retrotransposon in S. cerevisiae.
J. Berretta, M. Pinskaya, and A. Morillon (2008)
Genes & Dev. 22, 615-626
   Abstract »    Full Text »    PDF »
Chromodomains direct integration of retrotransposons to heterochromatin.
X. Gao, Y. Hou, H. Ebina, H. L. Levin, and D. F. Voytas (2008)
Genome Res. 18, 359-369
   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 »
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 »
Biogenesis and germline functions of piRNAs.
C. Klattenhoff and W. Theurkauf (2008)
Development 135, 3-9
   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 »
Argonaute 1 regulates the fate of germline stem cells in Drosophila.
L. Yang, D. Chen, R. Duan, L. Xia, J. Wang, A. Qurashi, P. Jin, and D. Chen (2007)
Development 134, 4265-4272
   Abstract »    Full Text »    PDF »
A novel class of bacteria-induced small RNAs in Arabidopsis.
S. Katiyar-Agarwal, S. Gao, A. Vivian-Smith, and H. Jin (2007)
Genes & Dev. 21, 3123-3134
   Abstract »    Full Text »    PDF »
The Piwi-piRNA Pathway Provides an Adaptive Defense in the Transposon Arms Race.
A. A. Aravin, G. J. Hannon, and J. Brennecke (2007)
Science 318, 761-764
   Abstract »    Full Text »    PDF »
Gene silencing mechanisms mediated by Aubergine piRNA complexes in Drosophila male gonad.
K. M. Nishida, K. Saito, T. Mori, Y. Kawamura, T. Nagami-Okada, S. Inagaki, H. Siomi, and M. C. Siomi (2007)
RNA 13, 1911-1922
   Abstract »    Full Text »    PDF »
Evolution of the bilaterian germ line: lineage origin and modulation of specification mechanisms.
C. G. M. Extavour (2007)
Integr. Comp. Biol. 47, 770-785
   Abstract »    Full Text »    PDF »
Characterization of Drosophila Telomeric Retroelement TAHRE: Transcription, Transpositions, and RNAi-based Regulation of Expression.
S. Shpiz, D. Kwon, A. Uneva, M. Kim, M. Klenov, Y. Rozovsky, P. Georgiev, M. Savitsky, and A. Kalmykova (2007)
Mol. Biol. Evol. 24, 2535-2545
   Abstract »    Full Text »    PDF »
The necessary junk: new functions for transposable elements.
A. R. Muotri, M. C.N. Marchetto, N. G. Coufal, and F. H. Gage (2007)
Hum. Mol. Genet. 16, R159-R167
   Abstract »    Full Text »    PDF »
siRNA-dependent and -independent post-transcriptional cosuppression of the LTR-retrotransposon MAGGY in the phytopathogenic fungus Magnaporthe oryzae.
T. Murata, N. Kadotani, M. Yamaguchi, Y. Tosa, S. Mayama, and H. Nakayashiki (2007)
Nucleic Acids Res. 35, 5987-5994
   Abstract »    Full Text »    PDF »
Drosophila PIWI associates with chromatin and interacts directly with HP1a.
B. Brower-Toland, S. D. Findley, L. Jiang, L. Liu, H. Yin, M. Dus, P. Zhou, S. C.R. Elgin, and H. Lin (2007)
Genes & Dev. 21, 2300-2311
   Abstract »    Full Text »    PDF »
The small interfering RNA production pathway is required for shoot meristem initiation in rice.
H. Nagasaki, J.-i. Itoh, K. Hayashi, K.-i. Hibara, N. Satoh-Nagasawa, M. Nosaka, M. Mukouhata, M. Ashikari, H. Kitano, M. Matsuoka, et al. (2007)
PNAS 104, 14867-14871
   Abstract »    Full Text »    PDF »
The mouse homolog of HEN1 is a potential methylase for Piwi-interacting RNAs.
Y. Kirino and Z. Mourelatos (2007)
RNA 13, 1397-1401
   Abstract »    Full Text »    PDF »
Repeat-associated siRNAs cause chromatin silencing of retrotransposons in the Drosophila melanogaster germline.
M. S. Klenov, S. A. Lavrov, A. D. Stolyarenko, S. S. Ryazansky, A. A. Aravin, T. Tuschl, and V. A. Gvozdev (2007)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
Cytotype Regulation by Telomeric P Elements in Drosophila melanogaster: Evidence for Involvement of an RNA Interference Gene.
M. J. Simmons, D.-F. Ryzek, C. Lamour, J. W. Goodman, N. E. Kummer, and P. J. Merriman (2007)
Genetics 176, 1945-1955
   Abstract »    Full Text »    PDF »
piRNAs--the ancient hunters of genome invaders.
J. V. Hartig, Y. Tomari, and K. Forstemann (2007)
Genes & Dev. 21, 1707-1713
   Abstract »    Full Text »    PDF »
Pimet, the Drosophila homolog of HEN1, mediates 2'-O-methylation of Piwi- interacting RNAs at their 3' ends.
K. Saito, Y. Sakaguchi, T. Suzuki, T. Suzuki, H. Siomi, and M. C. Siomi (2007)
Genes & Dev. 21, 1603-1608
   Abstract »    Full Text »    PDF »
A rapid, quantitative assay for direct detection of microRNAs and other small RNAs using splinted ligation.
P. A. Maroney, S. Chamnongpol, F. Souret, and T. W. Nilsen (2007)
RNA 13, 930-936
   Abstract »    Full Text »    PDF »
Transcription of the 1.688 Satellite DNA Family Is Under the Control of RNA Interference Machinery in Drosophila melanogaster Ovaries.
L. Usakin, J. Abad, V. V. Vagin, B. de Pablos, A. Villasante, and V. A. Gvozdev (2007)
Genetics 176, 1343-1349
   Abstract »    Full Text »    PDF »
A complex system of small RNAs in the unicellular green alga Chlamydomonas reinhardtii.
T. Zhao, G. Li, S. Mi, S. Li, G. J. Hannon, X.-J. Wang, and Y. Qi (2007)
Genes & Dev. 21, 1190-1203
   Abstract »    Full Text »    PDF »
The regulation of genes and genomes by small RNAs.
V. Ambros and X. Chen (2007)
Development 134, 1635-1641
   Abstract »    Full Text »    PDF »
piRNAs in the Germ Line.
H. Lin (2007)
Science 316, 397
   Abstract »    Full Text »    PDF »
Unique germ-line organelle, nuage, functions to repress selfish genetic elements in Drosophila melanogaster.
A. K. Lim and T. Kai (2007)
PNAS 104, 6714-6719
   Abstract »    Full Text »    PDF »
Carbodiimide-mediated cross-linking of RNA to nylon membranes improves the detection of siRNA, miRNA and piRNA by northern blot.
G. S. Pall, C. Codony-Servat, J. Byrne, L. Ritchie, and A. Hamilton (2007)
Nucleic Acids Res. 35, e60
   Abstract »    Full Text »    PDF »
The flamenco Locus Controls the gypsy and ZAM Retroviruses and Is Required for Drosophila Oogenesis.
M. Mevel-Ninio, A. Pelisson, J. Kinder, A. R. Campos, and A. Bucheton (2007)
Genetics 175, 1615-1624
   Abstract »    Full Text »    PDF »
A Slicer-Mediated Mechanism for Repeat-Associated siRNA 5' End Formation in Drosophila.
L. S. Gunawardane, K. Saito, K. M. Nishida, K. Miyoshi, Y. Kawamura, T. Nagami, H. Siomi, and M. C. Siomi (2007)
Science 315, 1587-1590
   Abstract »    Full Text »    PDF »
Critical roles for Dicer in the female germline.
E. P. Murchison, P. Stein, Z. Xuan, H. Pan, M. Q. Zhang, R. M. Schultz, and G. J. Hannon (2007)
Genes & Dev. 21, 682-693
   Abstract »    Full Text »    PDF »
Automated parallel isolation of multiple species of non-coding RNAs by the reciprocal circulating chromatography method.
K. Miyauchi, T. Ohara, and T. Suzuki (2007)
Nucleic Acids Res. 35, e24
   Abstract »    Full Text »    PDF »
A Novel Repeat-Associated Small Interfering RNA-Mediated Silencing Pathway Downregulates Complementary Sense gypsy Transcripts in Somatic Cells of the Drosophila Ovary.
A. Pelisson, E. Sarot, G. Payen-Groschene, and A. Bucheton (2007)
J. Virol. 81, 1951-1960
   Abstract »    Full Text »    PDF »
Secondary siRNAs Result from Unprimed RNA Synthesis and Form a Distinct Class.
T. Sijen, F. A. Steiner, K. L. Thijssen, and R. H. A. Plasterk (2007)
Science 315, 244-247
   Abstract »    Full Text »    PDF »
Eukaryotic regulatory RNAs: an answer to the 'genome complexity' conundrum.
K. V. Prasanth and D. L. Spector (2007)
Genes & Dev. 21, 11-42
   Abstract »    Full Text »    PDF »
Characterization of the short RNAs bound by the P19 suppressor of RNA silencing in mouse embryonic stem cells.
J. M. Calabrese and P. A. Sharp (2006)
RNA 12, 2092-2102
   Abstract »    Full Text »    PDF »
rasiRNAs, DNA Damage, and Embryonic Axis Specification.
W.E. THEURKAUF, C. KLATTENHOFF, D.P. BRATU, N. McGINNIS-SCHULTZ, B.S. KOPPETSCH, and H.A. COOK (2006)
Cold Spring Harb Symp Quant Biol 71, 171-180
   Abstract »    PDF »
Measuring the Rates of Transcriptional Elongation in the Female Drosophila melanogaster Germ Line by Nuclear Run-on.
A. SIGOVA, V. VAGIN, and P.D. ZAMORE (2006)
Cold Spring Harb Symp Quant Biol 71, 335-341
   Abstract »    PDF »
The Expanding Universe of Noncoding RNAs.
G.J. HANNON, F.V. RIVAS, E.P. MURCHISON, and J.A. STEITZ (2006)
Cold Spring Harb Symp Quant Biol 71, 551-564
   Abstract »    PDF »


To Advertise     Find Products

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