Michael D. Blower 1, 2, Maxence Nachury 1, 2, 3, Rebecca Heald 1, *, and Karsten Weis 1, *
1 Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720
* Correspondence: Rebecca Heald Ph: 510-643-5493;
F: 510-642-8620 [R.H.]
heald@socrates.berkeley.edu
* Correspondence: Karsten Weis Ph: 510-643-0407;
F: 510-643-6791 [K.W.]
kweis@berkeley.edu
2 These authors contributed equally to this work.
3 Present address: Department of Pathology, Stanford
University School of Medicine, Palo Alto, California 94305.
Centrosome-independent microtubule polymerization around chromosomes has been shown to require a local gradient of RanGTP, which discharges mitotic cargoes from the nuclear import receptor importin b. Here, we have used an activity-based assay in Xenopus egg extracts to purify the mRNA export protein Rae1 as a spindle assembly factor regulated by this pathway. Rae1 is a microtubule-associated protein that binds directly to importin b. Depletion of Rae1 from extracts or cells severely inhibits mitotic spindle assembly. A purified Rae1 complex stabilizes microtubules in egg extracts in a RanGTP/importin b-regulated manner. Interestingly, Rae1 exists in a large ribonucleoprotein complex, which requires RNA for its activity to control microtubule dynamics in vitro. Furthermore, we provide evidence that RNA associates with the mitotic spindle and that it plays a direct, translation-independent role in spindle assembly. Our studies reveal an unexpected function for RNA in spindle morphogenesis.
Supplementary data:
http://www.cell.com/cgi/content/full/121/2/223/DC1/
1. Chang P, Jacobson MK, and Mitchison TJ, "Poly(ADP-ribose) is required for spindle assembly and structure", Nature vol. 432, no. 7017, pp. 645 - 649 (02 December 2004).
2. Karsenti E, "Cytoskeleton: Spindle saga", Nature, vol. 432, no. 7017, pp. 563 - 564 (02 December 2004),
3. Frenster JH, "Nuclear polyanions as de-repressors of synthesis of Ribonucleic Acid", Nature, volume 206, number 4985, pp. 680 - 683 (15 May 1965).
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