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. pombe
mutants of dcr1
, the Dicer homolog, and
, 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
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
). Accordingly, we refer to these
from the successive cleavage of long dou-
). 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.
centromeric repeats (Fig. 1).
. 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
). 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 Arabidopsis
). DNA methylation, which isdownstream of H3 K9 methylation in Neu-rospora
), might be a consequence of
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
miRNAs are known to direct
function along with the centromeric central
References and Notes
translational repression of mRNA targets need-
). None of the RNAs match other
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ous plant and animal miRNAs are thought to
3. M. W. Rhoades et al.
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play similar roles in other contexts by target-
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4. N. C. Lau, L. P. Lim, E. G. Weinstein, D. P. Bartel,
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, 858 (2001).
5. M. Baum, V. K. Ngan, L. Clarke, Mol. Biol. Cell 5
). The ribonuclease III protein
Dicer is required for the processing of both
plete. Because S. pombe
6. N. Ayoub, I. Goldshmidt, R. Lyakhovetsky, A. Cohen,
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7. T. A. Volpe et al.
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Matzke, A. J. Matzke, EMBO J. 19
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domain of one centromere or from multiple
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10. Y. Nakaseko, Y. Adachi, S. Funahashi, O. Niwa, M.
Yanagida, EMBO J. 5
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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
In , million people died. Violence killed fewer than one million ofthem; famine contributed to about six million deaths; more than million died of some form of disease.1 Many of these illnesses were theresult primarily of old age and may have been unpreventable. That isunlikely to be true, however, of over a million deaths from malaria, nearlytwo million deaths from tuberc
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