Egg cytoplasm has the capability to reprogramme differentiated somatic nuclei, as shown by nuclear transplantation in animal cloning. The nucleoli of donor nuclei are rapidly disassembled on injection into interphase eggs and are correctly reassembled when donor transcription initiates in the early embryos of frogs and mammals, recapitulating the physiological nucleolar dynamics of early embryogenesis. This is one of the most remarkable structural reorganizations of somatic nuclei in nuclear cloning. Despite the long history of nuclear cloning, almost nothing is known about the molecular mechanism of nucleolar disassembly in egg cytoplasm. Here we show that the Xenopus germ cell proteins FRGY2a and FRGY2b reversibly disassemble somatic nucleoli in egg cytoplasm, independently of continuing ribosomal RNA transcription. The carboxy-terminal domain of FRGY2a, which localizes to the nucleoli, is sufficient for nucleolar disassembly in transfected cells. Our results show that a single protein fragment can trigger reversible disassembly of the complex nucleolar structure.
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ACKNOWLEDGEMENTS We thank M. Schmidt-Zachmann, M. O. J. Olson, B. McStay and J. G. Gall for antibodies and DNA probes; S. L. Erlandsen and G. Ahlstrand for electron microscopy; L. Higgins and T. Krick for mass spectrometry; and C. M. Verfaille, M. O. J. Olson and R. Kuriyama for comments. J.F. is supported by the University of Minnesota’s undergraduate research opportunities programme (UROP). This work was partly supported by the Minnesota Medical Foundation. N.K. wanted to show this work to Alan P. Wolffe, his previous mentor who first cloned FRGY2a but who passed away in a tragic accident on 26 May 2001, not knowing its nucleolar disassembly activity. Supplementary Information accompanies the paper on www.nature.com/naturecellbiology. Correspondence and requests for materials should be addressed to N.K.