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Molecular and Cellular Biology, November 2005, p. 9595-9607, Vol. 25, No. 21
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.21.9595-9607.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

PTB Regulates the Processing of a 3'-Terminal Exon by Repressing both Splicing and Polyadenylation

Caroline Le Sommer, Michelle Lesimple, Agnès Mereau, Severine Menoret, Marie-Rose Allo, and Serge Hardy*

UMR 6061 CNRS-Université de Rennes 1, IFR 140 Faculté de Médecine, CS 34317, 35043 Rennes Cedex, France

Received 19 May 2005/ Returned for modification 5 July 2005/ Accepted 1 August 2005

The polypyrimidine tract binding protein (PTB) has been described as a global repressor of regulated exons. To investigate PTB functions in a physiological context, we used a combination of morpholino-mediated knockdown and transgenic overexpression strategies in Xenopus laevis embryos. We show that embryonic endoderm and skin deficient in PTB displayed a switch of the {alpha}-tropomyosin pre-mRNA 3' end processing to the somite-specific pattern that results from the utilization of an upstream 3'-terminal exon designed exon 9A9'. Conversely, somitic targeted overexpression of PTB resulted in the repression of the somite-specific exon 9A9' and a switch towards the nonmuscle pattern. These results validate PTB as a key physiological regulator of the 3' end processing of the {alpha}-tropomyosin pre-mRNA. Moreover, using a minigene strategy in the Xenopus oocyte, we show that in addition to repressing the splicing of exon 9A9', PTB regulates the cleavage/polyadenylation of this 3'-terminal exon.


* Corresponding author. Mailing address: UMR 6061 CNRS-Université de Rennes 1, IFR 140 Faculté de Médecine, CS 34317, 35043 Rennes Cedex, France. Phone: 33 2 23 23 44 66. Fax: 33 2 23 23 44 78. E-mail: serge.hardy{at}univ-rennes1.fr.


Molecular and Cellular Biology, November 2005, p. 9595-9607, Vol. 25, No. 21
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.21.9595-9607.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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