The expression of poly(A)-binding protein gene is translationally regulated in a growth-dependent fashion through a 5 '-terminal oligopyrimidine tract motif

Poly(A) binding protein (PABP) is an important regulator of gene expression that has been implicated in control of translation initiation. Here we rep ort the isolation and the initial structural and functional characterizatio n of the human PABP gene. Delineation of the promoter region revealed that it directs the initiation of transcription at consecutive C residues within a stretch of pyrimidines. A study of the translational behavior of the cor responding mRNA demonstrates that it is translationally repressed upon grow th arrest of cultured mouse fibroblasts and translationally activated in re generating rat liver. Furthermore, transfection experiments show that the f irst 32 nucleotides of PABP mRNA are sufficient to confer growth-dependent translational control on a heterologous mRNA. Substitution of the C residue at the cap site by purines abolishes the translational control of the chim eric mRNA. These features have established PABP mRNA as a new member of the terminal oligopyrimidine tract mRNA family. Members of this family are kno wn to encode for components of the translational apparatus and to contain a n oligopyrimidine tract at the 5' terminus (5'TOP), This motif mediates the ir translational control in a growth-dependent manner.