Letter abstract
Nature Cell Biology 6, 784 - 791 (2004)
Published online: 11 July 2004 | doi:10.1038/ncb1155
Dicer is essential for formation of the heterochromatin structure in vertebrate cells
Tatsuo Fukagawa1, Masahiro Nogami1, Mitsuko Yoshikawa1, Masashi Ikeno2, Tuneko Okazaki2, Yasunari Takami3, Tatsuo Nakayama3 & Mitsuo Oshimura4
RNA interference is an evolutionarily conserved gene-silencing pathway in which the nuclease Dicer cleaves double-stranded RNA into small interfering RNAs1. The biological function of the RNAi-related pathway in vertebrate cells is not fully understood. Here, we report the generation of a conditional loss-of-function Dicer mutant in a chicken–human hybrid DT40 cell line that contains human chromosome 21. We show that loss of Dicer results in cell death with the accumulation of abnormal mitotic cells that show premature sister chromatid separation. Aberrant accumulation of transcripts from 
-satellite sequences, which consist of human centromeric repeat DNAs, was detected in Dicer-deficient cells. Immunocytochemical analysis revealed abnormalities in the localization of two heterochromatin proteins, Rad21 cohesin protein and BubR1 checkpoint protein, but the localization of core kinetochore proteins such as centromere protein (CENP)-A and -C was normal. We conclude that Dicer-related RNA interference machinery is involved in the formation of the heterochromatin structure in higher vertebrate cells.
- Precursory Research for Embryonic Science and Technology (PRESTO) of Japan Science and Technology Agency (JST), National Institute of Genetics and The Graduate University for Advanced Studies, Mishima, Shizuoka 411-8540, Japan.
- Institute of Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1101, Japan.
- Department of Biochemistry, Miyazaki Medical College, Kiyotake, Miyazaki 889-1692, Japan.
- Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Nishimachi 86, Yonago, Tottori 683-8503, Japan.
Correspondence to: Tatsuo Fukagawa1 e-mail: tfukagaw@lab.nig.ac.jp
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