Hairpin RNAs and Retrotransposon LTRs Effect RNAi and Chromatin-Based Gene Silencing
Abstract
The expression of short hairpin RNAs in several organisms silences gene expression by targeted mRNA degradation. This RNA interference (RNAi) pathway can also affect the genome, as DNA methylation arises at loci homologous to the target RNA in plants. We demonstrate in fission yeast that expression of a synthetic hairpin RNA is sufficient to silence the homologous locus in trans and causes the assembly of a patch of silent Swi6 chromatin with cohesin. This requires components of the RNAi machinery and Clr4 histone methyltransferase for small interfering RNA generation. A similar process represses several meiotic genes through nearby retrotransposon long terminal repeats (LTRs). These analyses directly implicate interspersed LTRs in regulating gene expression during cellular differentiation.
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We thank members of the Allshire lab for advice and suggestions; A. Pidoux, A. Bird, and N. Hastie for comments on the manuscript; T. Volpe and R. Martienssen for strains and discussions; A. Hamilton and M. Matzke for siRNA detection protocols. We are grateful to V. Wood and H. Levin for communicating data before publication. R.A. also thanks members of the Epigenetic Regulation Network (EC HPRN-CT-2000-00078) for valuable input especially T. Jenuwein for antiserum for methyl H3. This research is supported by the Wellcome Trust. R.A. is a Wellcome Trust Principal Research Fellow.
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Published In
Science
Volume 301 | Issue 5636
22 August 2003
22 August 2003
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American Association for the Advancement of Science.
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Received: 15 May 2003
Accepted: 7 July 2003
Published in print: 22 August 2003
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