The Prp19 complex directly functions in mitotic spindle assembly

The conserved Prp19 (pre-RNA processing 19) complex is required for pre-mRNA splicing in eukaryotic nuclei. Recent RNAi screens indicated that knockdown of Prp19 complex subunits strongly delays cell proliferation. Here we show that knockdown of the smallest subunit, BCAS2/Spf27, destabilizes the en...

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Bibliographic Details
Published in:PloS one 2013-09, Vol.8 (9), p.e74851-e74851
Main Authors: Hofmann, Jennifer C, Tegha-Dunghu, Justus, Dräger, Stefanie, Will, Cindy L, Lührmann, Reinhard, Gruss, Oliver J
Format: Article
Language:English
Subjects:
Animals
Artificial chromosomes
Biochemistry
Cell cycle
Cell division
Cell Line
Cell proliferation
Cells (Biology)
Chromosomes
Defects
DNA Repair Enzymes - genetics
DNA Repair Enzymes - metabolism
Gene expression
Gene Knockdown Techniques
Humans
Immunoglobulins
Interphase
Metaphase
Microtubules - metabolism
Mitosis
Mitosis - physiology
mRNA
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Nuclei
Proteins
Ribonucleic acid
RNA
RNA processing
RNA Splicing Factors
RNA-mediated interference
Screens
Spindle Apparatus - metabolism
Spindles
Splicing
Vertebrates
Xenopus
Xenopus laevis
Yang, Cindy
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Summary:The conserved Prp19 (pre-RNA processing 19) complex is required for pre-mRNA splicing in eukaryotic nuclei. Recent RNAi screens indicated that knockdown of Prp19 complex subunits strongly delays cell proliferation. Here we show that knockdown of the smallest subunit, BCAS2/Spf27, destabilizes the entire complex and leads to specific mitotic defects in human cells. These could result from splicing failures in interphase or reflect a direct function of the complex in open mitosis. Using Xenopus extracts, in which cell cycle progression and spindle formation can be reconstituted in vitro, we tested Prp19 complex functions during a complete cell cycle and directly in open mitosis. Strikingly, immunodepletion of the complex either before or after interphase significantly reduces the number of intact spindles, and increases the percentage of spindles with lower microtubule density and impaired metaphase alignment of chromosomes. Our data identify the Prp19 complex as the first spliceosome subcomplex that directly contributes to mitosis in vertebrates independently of its function in interphase.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0074851