Nucleoli come undone

The nucleolus is essential for ribosome synthesis, cell cycle control, and telomerase sequestration. This complex of rDNA, RNA, and proteins disassembles around ovulation and later reassembles during early embryogenesis. Somatic nuclei transplanted into eggs during nuclear cloning also undergo nucleolar disassembly and reassembly—processes that may contribute to the low efficiency of nuclear transplantation cloning. Now, Koichi Gonda, Nobuaki Kikyo, and colleagues (University of Minnesota, Minneapolis, MN) find that, despite their complexity, nucleoli need only a small RNA-binding protein to make them fall apart.

Gonda et al. purified two proteins from frog egg cytoplasm, FRGY2a and FRGY2b, that have nucleolar disassembly activity. Recombinant versions of either protein dispersed nucleolar proteins and RNA, leaving only small nucleolar remnants. FRGY2a/b may release proteins bound to RNA within the nucleoli through nonspecific competition, as regions imparting nonselective charge interactions with RNA were necessary for disassembly. Alternatively, they may target specific RNAs or RNA-protein particles, such as preribosomes. The latter argument is supported by the fact that mammalian nucleoli were not disassembled in frog eggs, although FRGY homologues have been identified in mouse and human cells.

The findings offer a simple biochemical method for studying nuclear remodeling during cloning as well as nucleolar assembly in general. The identification of RNAs or proteins that interact with FRGY2a/b should point to components necessary to maintain nucleoli. Nucleoli harbor certain cancer- and aging-related proteins, including p53-binding proteins and telomerase. “If we can understand how these proteins are localized or released by certain stimuli, we may be able to modify their localization for therapeutic applications,” says Kikyo. ▪

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