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J. Biol. Chem., Vol. 279, Issue 38, 39555-39564, September 17, 2004

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Alternative Polyadenylation Results in a Truncated daf-4 BMP Receptor That Antagonizes DAF-7-mediated Development in Caenorhabditis elegans^*

Cathy V. Gunther and Donald L. Riddle

From the Division of Biological Sciences, University of Missouri, Columbia, MO 65211

The DAF-4 receptor kinase, which promotes larval development, is encoded by a 2.9 kb mRNA transcribed from the only type II TGF-/BMP receptor gene in Caenorhabditis elegans. Here we report that alternative polyadenylation in intron 5 of daf-4 results in a 2.0 kb mRNA that encodes an open reading frame including only the N-terminal secretion signal and ligand-binding domains, and not the transmembrane or kinase domains, of DAF-4. Northern blots and real-time RT-PCR amplifications using RNA samples from developmentally staged animals show that expression levels of both the 2.9 kb and 2.0 kb transcripts are relatively constant, and their abundances similar, except for the transition between non-dauer and dauer stages. In dauer larvae, the steady-state level of the 2.0 kb mRNA increases more than 10-fold and exceeds the 2.9 kb transcript, coincident with an absence of signaling from DAF-4. Transgenic expression of a recombinant daf-4 transgene that encodes only the 2.0 kb mRNA enhances the Daf-c phenotype of a daf-4 hypomorph, whereas the same transgene with a nonsense mutation does not. These data suggest that a polypeptide encoded by the 2.0 kb transcript can function as an antagonist of full-length DAF-4 signaling. Alternative processing of type II receptor transcripts to generate an antagonist is a novel mechanism for negative regulation of a TGF- signaling pathway.

Received for publication, July 7, 2004

^* This work was supported by Department of Health and Human Services Grant GM60151 (to D. L. R.). 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 a Supplementary figure.

Recipient of NRSA GM17491.

To whom correspondence should be addressed. Tel.: 573-882-6363; Fax: 573-884-9676; E-mail: riddled{at}missouri.edu.

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