The Drosophila Poly(A) Binding Protein-Interacting Protein, dPaip2, Is a Novel Effector of Cell Growth

Abstract

The 3′ poly(A) tail of eukaryotic mRNAs and the poly(A) binding protein (PABP) play important roles in the regulation of translation. Recently, a human PABP-interacting protein, Paip2, which disrupts the PABP-poly(A) interaction and consequently inhibits translation, was described. To gain insight into the biological role of Paip2, we studied the Drosophila melanogaster Paip2 (dPaip2). dPaip2 is the bona fide human Paip2 homologue, as it interacts with dPABP, inhibits binding of dPABP to the mRNA poly(A) tail, and reduces translation of a reporter mRNA by ∼80% in an S2 cell-free translation extract. Ectopic overexpression of dPaip2 in Drosophila wings and wing discs results in a size reduction phenotype, which is due to a decrease in cell number. Clones of cells overexpressing dPaip2 in wing discs also contain fewer cells than controls. This phenotype can be explained by a primary effect on cell growth. Indeed, overexpression of dPaip2 in postreplicative tissues inhibits growth, inasmuch as it reduces ommatidia size in eyes and cell size in the larval fat body. We conclude that dPaip2 inhibits cell growth primarily by inhibiting protein synthesis.

We thank C. Lister and C. Binda for technical assistance and A. Kahvejian, Y. Svitkin, H. Imataka, J. Berlanga, A. Brasey, J. Dostie, and A. Brueschke for helpful discussions. We are grateful to S. J. Leevers, T. Radimerski, and A. Brueschke for critical reading of the manuscript. We are indebted to V. Evdokimova for her advice. We thank C. DeMaria for preparation of the pBac-His-HMK-dPABP, pGST-dPABP, and pET-His-HMK-dPABP plasmids. We thank C. M. Schuster and the Bloomington Stock Center for providing the UAS-dPABP and P(10970) fly lines, respectively.

This research was supported by grants from the National Institutes of Health (1 RO1 GM66157-01) to N.S. and from the Canadian Institute of Health Research (CIHR) to N.S. and P.L. N.S. is a CIHR Distinguished Scientist, a Howard Hughes Medical Institute International Scholar, and a James McGill Professor. P.L. is a CIHR Investigator. G.R. and K.K. were recipients of doctoral studentships from the CIHR. M.M. was the recipient of a doctoral studentship from the Cancer Research Society. G.R. was the recipient of a McGill Major Studentship and now holds a McGill Faculty of Medicine internal studentship.