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Published online
doi:10.1083/jcb.200703133
The Journal of Cell Biology, Vol. 179, No. 4, 601-609
The Rockefeller University Press, 0021-9525 $30.00
© Montembault et al.
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PRP4 is a spindle assembly checkpoint protein required for MPS1, MAD1, and MAD2 localization to the kinetochores



Emilie Montembault1,2, Stéphanie Dutertre2, Claude Prigent1,2, and Régis Giet1,2

1 Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6061, Université de Rennes I, Institut de Génétique et Développement, 35043 Rennes, France
2 Institut Fédératif De Recherche 140, Génomique Fonctionelle Agronomie Santé, Plateforme Microscopie, Faculté de Médecine, 35043 Rennes, France

Correspondence to Claude Prigent: claude.prigent{at}univ-rennes1.fr; or Régis Giet: regis.giet{at}univ-rennes1.fr

The spindle checkpoint delays anaphase onset until every chromosome kinetochore has been efficiently captured by the mitotic spindle microtubules. In this study, we report that the human pre–messenger RNA processing 4 (PRP4) protein kinase associates with kinetochores during mitosis. PRP4 depletion by RNA interference induces mitotic acceleration. Moreover, we frequently observe lagging chromatids during anaphase leading to aneuploidy. PRP4-depleted cells do not arrest in mitosis after nocodazole treatment, indicating a spindle assembly checkpoint (SAC) failure. Thus, we find that PRP4 is necessary for recruitment or maintenance of the checkpoint proteins MPS1, MAD1, and MAD2 at the kinetochores. Our data clearly identify PRP4 as a previously unrecognized kinetochore component that is necessary to establish a functional SAC.

Abbreviations used in this paper: APC/C, anaphase-promoting complex/ cyclosome; CENP-A, centromere protein A; NEBD, nuclear envelope breakdown; SAC, spindle assembly checkpoint.


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