The Drosophila poly(A) binding protein-interacting protein, dPaip2, is a novel effector of cell growth.
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 approximately 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.
Roy
Guylaine
G
Department of Biochemistry and McGill Cancer Centre, McGill University, Montréal, Québec H3G 1Y6, Canada.
Miron
Mathieu
M
Khaleghpour
Kianoush
K
Lasko
Paul
P
Sonenberg
Nahum
N
D000241:Adenosine / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D005123:Eye / Q000254:growth & development; D005216:Fat Body / Q000378:metabolism; D007814:Larva / Q000378:metabolism; D008969:Molecular Sequence Data; D039102:Poly(A)-Binding Proteins; D011108:Polymers / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*
D002352:Carrier Proteins; D029721:Drosophila Proteins; C481795:Paip2 protein, Drosophila; D039102:Poly(A)-Binding Proteins; D011108:Polymers; D012333:RNA, Messenger; C069424:polyadenosine; D000241:Adenosine