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J. Biol. Chem., Vol. 283, Issue 45, 31256-31267, November 7, 2008

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Drosophila MFAP1 Is Required for Pre-mRNA Processing and G₂/M Progression^*

From the Apoptosis and Proliferation Control Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom

The mammalian spliceosome has mainly been studied using proteomics. The isolation and comparison of different splicing intermediates has revealed the dynamic association of more than 200 splicing factors with the spliceosome, relatively few of which have been studied in detail. Here, we report the characterization of the Drosophila homologue of microfibril-associated protein 1 (dMFAP1), a previously uncharacterized protein found in some human spliceosomal fractions ( Jurica, M. S., and Moore, M. J. (2003) Mol. Cell 12, 5-14[CrossRef][Medline] [Order article via Infotrieve] ). We show that dMFAP1 binds directly to the Drosophila homologue of Prp38p (dPrp38), a tri-small nuclear ribonucleoprotein component ( Xie, J., Beickman, K., Otte, E., and Rymond, B. C. (1998) EMBO J. 17, 2938-2946[CrossRef][Medline] [Order article via Infotrieve] ), and is required for pre-mRNA processing. dMFAP1, like dPrp38, is essential for viability, and our in vivo data show that cells with reduced levels of dMFAP1 or dPrp38 proliferate more slowly than normal cells and undergo apoptosis. Consistent with this, double-stranded RNA-mediated depletion of dPrp38 or dMFAP1 causes cells to arrest in G₂/M, and this is paralleled by a reduction in mRNA levels of the mitotic phosphatase string/cdc25. Interestingly double-stranded RNA-mediated depletion of a wide range of core splicing factors elicits a similar phenotype, suggesting that the observed G₂/M arrest might be a general consequence of interfering with spliceosome function.

Received for publication, May 8, 2008 , and in revised form, September 2, 2008.

^* This work was supported by Cancer Research UK. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S3.

¹ To whom correspondence should be addressed: P. O. Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX United Kingdom. Tel.: 0044-207-269-3635; Fax: 0044-207-269-3638; E-mail: nicolas.tapon{at}cancer.org.uk.

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