MOLECULAR BIOLOGY: Chromosome Structure

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Science  30 Jul 2004:
Vol. 305, Issue 5684, pp. 575b
DOI: 10.1126/science.305.5684.575b

RNA interference (RNAi) has been linked with heterochromatin formation, gene silencing, and chromosome segregation in fission yeast. Transcripts from the outer centromere repeats of the yeast chromosomes are chopped up by the RNAi machinery, forming small interfering (si)RNAs, which are required for the formation of heterochromatin over the outer repeats. In RNAi mutants, heterochromatin fails to form over the repeats, perturbing the binding of cohesin to the centromeres. This affects sister chromatid cohesion in mitosis and hence prevents the proper segregation of the chromosomes during cell division.

Does RNAi have a similar role in vertebrates? Fukagawa et al. have addressed this question by making a conditional knockout of Dicer, the enzyme that cleaves double-stranded RNAs to generate siRNAs, in a chicken cell line that also contains a single copy of human chromosome 21. Cells lacking Dicer, and therefore RNAi, showed transcription of both strands of centromeric repeat DNA, in a manner somewhat reminiscent of fission yeast, as well as the possible presence of repeat-derived small RNAs in wild-type cells. Furthermore, in Dicer-deficient cells, binding of HP1 proteins, central components of heterochromatin, was perturbed at the centromeres. Finally, these cells showed defective sister chromatid cohesion of human chromosome 21, as well as of the chicken chromosomes, and substantial mis-segregation of the human chromosome, suggesting that RNAi may indeed play a role in heterochromatin formation at centromeres in vertebrates. — GR

Nature Cell Biol. 10.1038/ncb1155 (2004).

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