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Tissue-specific autoregulation of Drosophila suppressor of forked by alternative poly(A) site utilization leads to accumulation of the suppressor of forked protein in mitotically active cells

Published online by Cambridge University Press:  08 December 2000

FRANÇOIS JUGE
Affiliation:
Génétique du Développement de la Drosophile, Institut de Génétique Humaine, 34396 Montpellier Cedex 5, France
AGNÈS AUDIBERT
Affiliation:
Génétique du Développement de la Drosophile, Institut de Génétique Humaine, 34396 Montpellier Cedex 5, France Present address: Institut de Recherches sur le Cancer, 7 rue Guy Moquet, 94801 Villejuif, France.
BÉATRICE BENOIT
Affiliation:
Génétique du Développement de la Drosophile, Institut de Génétique Humaine, 34396 Montpellier Cedex 5, France
MARTINE SIMONELIG
Affiliation:
Génétique du Développement de la Drosophile, Institut de Génétique Humaine, 34396 Montpellier Cedex 5, France
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Abstract

The Suppressor of forked protein is the Drosophila homolog of the 77K subunit of human cleavage stimulation factor, a complex required for the first step of the mRNA 3′-end-processing reaction. We have shown previously that wild-type su(f) function is required for the accumulation of a truncated su(f) transcript polyadenylated in intron 4 of the gene. This led us to propose a model in which the Su(f) protein would negatively regulate its own accumulation by stimulating 3′-end formation of this truncated su(f) RNA. In this article, we demonstrate this model and show that su(f) autoregulation is tissue specific. The Su(f) protein accumulates at a high level in dividing tissues, but not in nondividing tissues. We show that this distribution of the Su(f) protein results from stimulation by Su(f) of the tissue-specific utilization of the su(f) intronic poly(A) site, leading to the accumulation of the truncated su(f) transcript in nondividing tissues. Utilization of this intronic poly(A) site is affected in a su(f) mutant and restored in the mutant with a transgene encoding wild-type Su(f) protein. These data provide an in vivo example of cell-type-specific regulation of a protein level by poly(A) site choice, and confirm the role of Su(f) in regulation of poly(A) site utilization.

Type
Research Article
Copyright
2000 RNA Society

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