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J. Biol. Chem., Vol. 279, Issue 16, 16571-16580, April 16, 2004

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Proteolytic Processing and Translation Initiation

TWO INDEPENDENT MECHANISMS FOR THE EXPRESSION OF THE SENDAI VIRUS Y PROTEINS^*

Sylvain de Breyne, Romaine Stalder Monney, and Joseph Curran

From the Department of Microbiology and Molecular Medicine, The University of Geneva Medical School (Centre Médicale Universitaire), 1 rue Michel Servet, CH-1211 Geneva 4, Switzerland

The four Sendai virus C-proteins (C', C, Y1, and Y2) represent an N-terminal nested set of non-structural proteins whose expression modulates both the readout of the viral genome and the host cell response. In particular, they modulate the innate immune response by perturbing the signaling of type 1 interferons. The initiation codons for the four C-proteins have been mapped in vitro, and it has been proposed that the Y proteins are initiated by ribosomal shunting. A number of mutations were reported that significantly enhanced Y expression, and this was attributed to increased shunt-mediated initiation. However, we demonstrate that this arises due to enhanced proteolytic processing of C', an event that requires its very N terminus. Curiously, although Y expression in vitro is mediated almost exclusively by initiation, Y proteins in vivo can arise both by translation initiation and processing of the C' protein. To our knowledge this is the first example of two apparently independent pathways leading to the expression of the same polypeptide chain. This dual pathway explains several features of Y expression.

Received for publication, November 12, 2003 , and in revised form, January 8, 2004.

^* This work was supported by Swiss Science Foundation Grants 31-57434.99 and 3100A0-100221. 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.

To whom correspondence should be addressed. Tel.: 41-22-3795655; E-mail: Joseph.Curran{at}medecine.unige.ch.

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