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strands of the repeat region (Fig. 1). In- deed, Volpe et al. report in this issue thattranscripts are produced from both strands of the dh repeat, and these transcripts mark-edly increase in abundance in S. pombemutants of dcr1, the Dicer homolog, and ago1, the Argonaute homolog (7 ). Most ofour centromeric small RNAs cluster within or near these transcripts, suggesting thatRNAs produced from each strand of therepeat anneal to form dsRNA that is yeast. To investigate this possibility, we cleaved by Dicer into the small RNAs (7 ).
croRNAs (miRNAs) are two types of ϳ22– Mutations in dcr1 and ago1 in S. pombe tially growing S. pombe using a method important roles as regulators of gene ex- pression in eukaryotes (1). siRNAs derive of Dicer cleavage products, i.e., ϳ22-nt function (7 ). Accordingly, we refer to these from the successive cleavage of long dou- groups (4 ). Of 61 sequenced clones, 49 and suggest that they specify the epigenetic targets during RNA interference in animals ground in such cloning efforts. Each of the remaining 12 sequences matched the S. pombe centromeric repeats (Fig. 1).
Neurospora. miRNAs are processed from regulate expression levels of cell fate de- endogenous hairpin transcripts such that a are from the dh repeat, an element that can confer heterochromatic silencing on anoth- each hairpin molecule. Certain Caenorhab- er locus and is sufficient for centromere in unicellular yeast (1, 3). EndogenoussiRNAs that could cleave complementarymRNAs are also described in plants andanimals. However, other cloned RNAs donot fall into these two classes and might beheterochromatic siRNAs. In fact, epigenet-ic modifications have been correlated withsmall RNAs in multicellular eukaryotes,such as methylation of promoter DNA dur-ing transcriptional silencing of Arabidopsistransgenes (8). DNA methylation, which isdownstream of H3 K9 methylation in Neu-rospora (9), might be a consequence of Fig. 1. Heterochromatic siRNAs (sequences A through L) from S. pombe. The loci and
orientation of matches to representative repeats are indicated below each centromere methylation. Therefore, sequence-specific fragment. Sequence K only matches ChrIII, and sequences D, E, and L match other repeats on targeting of histone modifications could be ChrIII. Centromeric repeats (10) are in green (dg) and orange (dh). Although the innermost centromeric repeats contain tRNA sequences, all tRNA fragments that were cloned map ditis elegans miRNAs are known to direct function along with the centromeric central References and Notes
translational repression of mRNA targets need- core (5, 6 ). None of the RNAs match other 1. G. Hutva´gner, P. D. Zamore, Curr. Opin. Genet. Dev. ed for proper larval development, and numer- heterochromatic regions, such as the cen- 12, 225 (2002).
2. E. C. Lai, Nature Genet. 30, 363 (2002).
ous plant and animal miRNAs are thought to 3. M. W. Rhoades et al., Cell, 110, 513 (2002).
play similar roles in other contexts by target- sequences, or the mating type locus region 4. N. C. Lau, L. P. Lim, E. G. Weinstein, D. P. Bartel, ing mRNAs for translation attenuation or de- homologous to the dh repeat, although our Science 294, 858 (2001).
5. M. Baum, V. K. Ngan, L. Clarke, Mol. Biol. Cell 5, 747
struction (1–3). The ribonuclease III protein Dicer is required for the processing of both plete. Because S. pombe centromeres are 6. N. Ayoub, I. Goldshmidt, R. Lyakhovetsky, A. Cohen, large regions (40 to 100 kb) with homolo- Genetics 156, 983 (2000).
7. T. A. Volpe et al., Science 297, XXX (2002).
8. M. F. Mette, W. Aufsatz, J. van der Winden, M. A.
domain) proteins, whose biochemical func- Matzke, A. J. Matzke, EMBO J. 19, 5194 (2000).
tions are unclear, are also necessary for pro- domain of one centromere or from multiple 9. H. Tamaru, E. U. Selker, Nature 414, 277 (2001).
10. Y. Nakaseko, Y. Adachi, S. Funahashi, O. Niwa, M.
Yanagida, EMBO J. 5, 1011 (1986).
11. We thank T. Volpe et al. for sharing results before in that transcription of adjacent genomic found in the genome of Schizosaccharomy- Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. E-mail: www.sciencemag.org SCIENCE VOL 297 13 SEPTEMBER 2002

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