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J. Biol. Chem., Vol. 283, Issue 21, 14845-14856, May 23, 2008

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Mitotic Functions for SNAP45, a Subunit of the Small Nuclear RNA-activating Protein Complex SNAP_c^*

Mayilvahanan Shanmugam and Nouria Hernandez¹

From the Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 and the Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Génopode Building, 1015 Lausanne, Switzerland

The small nuclear RNA-activating protein complex SNAP_c is required for transcription of small nuclear RNA genes and binds to a proximal sequence element in their promoters. SNAP_c contains five types of subunits stably associated with each other. Here we show that one of these polypeptides, SNAP45, also known as PTF , localizes to centrosomes during parts of mitosis, as well as to the spindle midzone during anaphase and the mid-body during telophase. Consistent with localization to these mitotic structures, both down- and up-regulation of SNAP45 lead to a G₂/M arrest with cells displaying abnormal mitotic structures. In contrast, down-regulation of SNAP190, another SNAP_c subunit, leads to an accumulation of cells with a G₀/G₁ DNA content. These results are consistent with the proposal that SNAP45 plays two roles in the cell, one as a subunit of the transcription factor SNAP_c and another as a factor required for proper mitotic progression.

Received for publication, January 31, 2008 , and in revised form, March 20, 2008.

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^* This work was supported, in whole or in part, by National Institutes of Health Grant GM38810. This work was also supported by the Howard Hughes Medical Institute and by Swiss National Science Foundation Grant 3100A0-109941/1. 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-S6.

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¹ To whom correspondence should be addressed: Center for Integrative Genomics, University of Lausanne, Génopode Bldg., Quartier Sorge, 1015 Lausanne, Switzerland. Fax: 41-21-692-3925; E-mail: Nouria.Hernandez{at}unil.ch.

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