title: PRP4 is a spindle assembly checkpoint protein required for MPS1, MAD1, and MAD2 localization to the kinetochores.
abstract: 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.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6061, Université de Rennes I, Institut de Génétique et Développement, 35043 Rennes, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Montembault
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dutertre
authors.forename: Claude
authors.initials: C
authors.lastname: Prigent
authors.forename: Régis
authors.initials: R
authors.lastname: Giet
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D064246:Mad2 Proteins; D008667:Metalloproteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012269:Ribosomal Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000502:physiology*; D019076:Transgenes
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C501384:MAD1L1 protein, human; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D008667:Metalloproteins; D009687:Nuclear Proteins; C489982:PRPF4 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C083686:RPS27 protein, human; D011994:Recombinant Proteins; D012097:Repressor Proteins; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D012269:Ribosomal Proteins; D049452:Green Fluorescent Proteins