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Originally published In Press as doi:10.1074/jbc.M200500200 on March 23, 2002

J. Biol. Chem., Vol. 277, Issue 22, 19511-19520, May 31, 2002
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A Common Mechanism of Stage-regulated Gene Expression in Leishmania Mediated by a Conserved 3'-Untranslated Region Element*

Nathalie BoucherDagger §, Ying WuDagger , Carole Dumas, Marthe Dubé, Denis Sereno, Marie Breton§, and Barbara Papadopoulou||

From the Centre de Recherche en Infectiologie du Centre de Recherche du Centre Hospitalier de Université Laval and the Département de Biologie Médicale, Faculté de Médecine, Université Laval, Québec G1V 4G2, Canada

Developmental regulation of mRNA levels in trypanosomatid protozoa is determined post-transcriptionally and often involves sequences located in the 3'-untranslated regions (3'-UTR) of the mRNAs. We have previously identified a developmentally regulated gene family in Leishmania encoding the amastin surface proteins and showed that stage-specific accumulation of the amastin mRNA is mediated by sequences within the 3'-UTR. Here we identified a 450-nt region within the amastin 3'-UTR that can confer amastigote-specific gene expression by a novel mechanism that increases mRNA translation without an increase in mRNA stability. Remarkably, this 450-nt 3'-UTR element is highly conserved among a large number of Leishmania mRNAs in several Leishmania species. Here we show that several of these mRNAs are differentially expressed in the intracellular amastigote stage of the parasite and that the 450-nt conserved element in their 3'-UTRs is responsible for stage-specific gene regulation. We propose that the 450-nt conserved element, which is unlike any other regulatory element identified thus far, is part of a common mechanism of stage-regulated gene expression in Leishmania that regulates mRNA translation in response to intracellular stresses.

* This work was supported by Canadian Institutes of Health Research Grant gr-14500 (to B. P.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger These authors contributed equally to this work.

§ Recipient of a Canadian Institutes of Health Research studentship.

Present address: Laboratoire de Biologie Parasitaire, Institut de Recherche pour le Développement, Montpellier, France.

|| Member of a Canadian Institutes of Health Research group on host-pathogen interactions. Fonds de Recherche en Santé de Québec Senior Scholar. Burroughs Wellcome Fund New Investigator in Molecular Parasitology. To whom correspondence should be addressed: Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, 2705 boul. Laurier, Ste-Foy, Québec G1V 4G2, Canada. Tel.: 418-654-2705; Fax: 418-654-2715; E-mail: barbara.papadopoulou@crchul.ulaval.ca.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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