Roy Guylaine, Miron Mathieu, Khaleghpour Kianoush, Lasko Paul, Sonenberg Nahum
Department of Biochemistry and McGill Cancer Centre, McGill University, Montréal, Québec H3G 1Y6, Canada.
Mol Cell Biol. 2004 Feb;24(3):1143-54. doi: 10.1128/MCB.24.3.1143-1154.2004.
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.
真核生物信使核糖核酸（mRNA）的3' 聚腺苷酸（poly(A)）尾和聚腺苷酸结合蛋白（PABP）在翻译调控中发挥着重要作用。最近，一种能破坏PABP与poly(A)相互作用并因此抑制翻译的人类PABP相互作用蛋白Paip2被报道。为深入了解Paip2的生物学作用，我们研究了果蝇的Paip2（dPaip2）。dPaip2是真正的人类Paip2同源物，因为它与dPABP相互作用，抑制dPABP与mRNA poly(A)尾的结合，并在S2无细胞翻译提取物中将报告mRNA的翻译减少约80%。dPaip2在果蝇翅膀和翅盘中异位过表达会导致尺寸减小的表型，这是由于细胞数量减少所致。在翅盘中过表达dPaip2的细胞克隆也比对照含有更少的细胞。这种表型可以通过对细胞生长的主要影响来解释。实际上, 在复制后组织中过表达dPaip2会抑制生长，因为它会减小眼睛中小眼的尺寸和幼虫脂肪体中的细胞大小。我们得出结论，dPaip2主要通过抑制蛋白质合成来抑制细胞生长。
