A Genome-Wide Screen Identifies 27 Genes Involved in Transposon Silencing in C. elegans

Transposon jumps are a major cause of genome instability. In the C. elegans strain Bristol N2, transposons are active in somatic cells, but they are silenced in the germline, presumably to protect the germline from mutations. Interestingly, the transposon-silencing mechanism shares factors with the RNAi machinery. To better understand the mechanism of transposon silencing, we performed a genome-wide RNAi screen for genes that, when silenced, cause transposition of Tc1 in the C. elegans germline. We identified 27 such genes, among which are mut-16, a mutator that was previously found but not identified at the molecular level, ppw-2, a member of the argonaute family, and several factors that indicate a role for chromatin structure in the regulation of transposition. Some of the newly identified genes are also required for cosuppression and therefore represent the shared components of the two pathways. Since most of the newly identified genes have clear homologs in other species, and since transposons are found from protozoa to human, it seems likely that they also protect other genomes against transposon activity in the germline.

[1]  A. Pasquinelli,et al.  Genes and Mechanisms Related to RNA Interference Regulate Expression of the Small Temporal RNAs that Control C. elegans Developmental Timing , 2001, Cell.

[2]  T. Kakutani,et al.  Mobilization of transposons by a mutation abolishing full DNA methylation in Arabidopsis , 2001, Nature.

[3]  U. K. Laemmli,et al.  Chromatin Boundaries in Budding Yeast The Nuclear Pore Connection , 2002, Cell.

[4]  Titia Sijen,et al.  RNA Helicase MUT-14-Dependent Gene Silencing Triggered in C. elegans by Short Antisense RNAs , 2002, Science.

[5]  R. Plasterk,et al.  The silence of the genes. , 2000, Current opinion in genetics & development.

[6]  W. G. Kelly,et al.  Chromatin silencing and the maintenance of a functional germline in Caenorhabditis elegans. , 1998, Development.

[7]  Michael Q. Zhang,et al.  The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. , 2002, Genes & development.

[8]  B. Saari,et al.  Activation of a transposable element in the germ line but not the soma of Caenorhabditis elegans , 1987, Nature.

[9]  P. Zipperlen,et al.  Functional genomic analysis of C. elegans chromosome I by systematic RNA interference , 2000, Nature.

[10]  R. Plasterk,et al.  Continuous exchange of sequence information between dispersed Tc1 transposons in the Caenorhabditis elegans genome. , 2003, Genetics.

[11]  A. Villeneuve,et al.  Transgene-mediated cosuppression in the C. elegans germ line. , 2000, Genes & development.

[12]  Sebastian A. Leidel,et al.  Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III , 2000, Nature.

[13]  Yuji Kohara,et al.  Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi , 2001, Current Biology.

[14]  Y. Dong,et al.  Systematic functional analysis of the Caenorhabditis elegans genome using RNAi , 2003, Nature.

[15]  R. Waterston,et al.  Molecular cloning of the muscle gene unc-22 in Caenorhabditis elegans by Tc1 transposon tagging. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[16]  G. Macino,et al.  Involvement of small RNAs and role of the qde genes in the gene silencing pathway in Neurospora. , 2002, Genes & development.

[17]  R. Plasterk,et al.  mut-7 of C. elegans, Required for Transposon Silencing and RNA Interference, Is a Homolog of Werner Syndrome Helicase and RNaseD , 1999, Cell.

[18]  H. Cerutti,et al.  Suppressors of transcriptional transgenic silencing in Chlamydomonas are sensitive to DNA-damaging agents and reactivate transposable elements , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[19]  A. Caudy,et al.  Role for a bidentate ribonuclease in the initiation step of RNA interference , 2001 .

[20]  Andrew Smith Genome sequence of the nematode C-elegans: A platform for investigating biology , 1998 .

[21]  R. Martienssen,et al.  Robertson's Mutator transposons in A. thaliana are regulated by the chromatin-remodeling gene Decrease in DNA Methylation (DDM1). , 2001, Genes & development.

[22]  J. Labbé,et al.  Using RNA interference to identify genes required for RNA interference , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[23]  V. Ambros,et al.  MicroRNAs and Other Tiny Endogenous RNAs in C. elegans , 2003, Current Biology.

[24]  R. Waterston,et al.  Transposable element Tc1 of Caenorhabditis elegans recognizes specific target sequences for integration. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Andrew Fire,et al.  The rde-1 Gene, RNA Interference, and Transposon Silencing in C. elegans , 1999, Cell.

[26]  Y. Jiang Transcriptional cosuppression of yeast Ty1 retrotransposons. , 2002, Genes & development.

[27]  G. Hannon,et al.  C . elegans involved in developmental timing in Dicer functions in RNA interference and in synthesis of small RNA , 2001 .

[28]  E. Schulze,et al.  A single histone H1 isoform (H1.1) is essential for chromatin silencing and germline development in Caenorhabditis elegans. , 2001, Development.

[29]  S. Hammond,et al.  An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells , 2000, Nature.

[30]  A. Caudy,et al.  Argonaute2, a Link Between Genetic and Biochemical Analyses of RNAi , 2001, Science.

[31]  Ronald H. A. Plasterk,et al.  A genetic link between co-suppression and RNA interference in C. elegans , 2000, Nature.

[32]  S. R. Wicks,et al.  CHE-3, a cytosolic dynein heavy chain, is required for sensory cilia structure and function in Caenorhabditis elegans. , 2000, Developmental biology.

[33]  S. W. Emmons,et al.  High-frequency excision of transposable element Tc1 in the nematode caenorhabditis elegans is limited to somatic cells , 1984, Cell.

[34]  R. Plasterk,et al.  PPW-1, a PAZ/PIWI Protein Required for Efficient Germline RNAi, Is Defective in a Natural Isolate of C. elegans , 2002, Current Biology.

[35]  Henning Urlaub,et al.  Single-Stranded Antisense siRNAs Guide Target RNA Cleavage in RNAi , 2002, Cell.