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J. Biol. Chem., Vol. 281, Issue 51, 39135-39141, December 22, 2006

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The Drosophila Heterogeneous Nuclear Ribonucleoprotein M Protein, HRP59, Regulates Alternative Splicing and Controls the Production of Its Own mRNA^*

From the Department of Molecular Biology and Functional Genomics, Stockholm University SE-10691, Stockholm, Sweden

The Drosophila heterogeneous nuclear ribonucleoprotein M, HRP59, is a nuclear protein that associates co-transcriptionally with pre-mRNA and is necessary for the correct expression of a subset of mRNAs. We show here that the hrp59 pre-mRNA is alternatively spliced to generate two different mRNAs that differ in the presence of exon 3. Exon 3-containing transcripts make up the majority of hrp59 transcripts and encode for the functional protein, HRP59-1. Transcripts that lack exon 3 contain a premature translation termination codon and are targeted to the nonsense mediated decay pathway. We show that exon 3 inclusion is itself inhibited by HRP59 and that changes in the HRP59 protein levels affect the splicing activity of the cell. We propose that the ability of HRP59 to regulate the alternative splicing of its own pre-mRNA serves in a negative feedback loop that controls the levels of the HRP59 protein and maintains the homeostasis of the splicing environment.

Received for publication, May 3, 2006 , and in revised form, October 30, 2006.

^* This work was supported by the Swedish Research Council. 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 data.

¹ Recipient of a postdoctoral stipend from the Carl Trygger Foundation. To whom correspondence should be addressed. Tel.: 46-8-6747810; Fax: 46-8-166488; E-mail: manuela.hase{at}biosci.ki.se.

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