Substitution of just five nucleotides at and around the transcription start site of rat β-actin promoter is sufficient to render the resulting transcript a subject for translational control

Vertebrate mRNAs with a 5' terminal oligopyrimidine tract (5' TOP), including those encoding ribosomal proteins and elongation factors, are candidates for translational control in a growth-dependent fashion. The present study was designed to determine the minimal cis-regulatory element involved in this mode of regulation. We selected rat p-actin mRNA, a typical translationally uncontrolled transcript, as a subject for gain-of-function analysis. Mutations at and around its cap site leading to the formation of a 7 pyrimidines long 5' TOP render the resulting transcript translationally repressed upon growth arrest of lymphosarcoma cells. In contrast, growth-dependent translational control of this mRNA in fibroblasts requires, in addition, a GC motif downstream of the 5' TOP, A similar motif is present in all ribosomal protein mRNAs shown to be translationally controlled.