THE 5'-TERMINAL-OLIGOPYRIMIDINE-TRACT CONFERS TRANSLATIONAL CONTROL ON TOP MESSENGER-RNAS IN A CELL-TYPE AND SEQUENCE CONTEXT-DEPENDENT MANNER

TOP mRNAs are vertebrate transcripts which contain a 5' terminal oligo pyrimidine tract (5' TOP), encode for ribosomal proteins and elongatio n factors 1 alpha and 2, and are candidates for growth-dependent trans lational control mediated through their 5' TOP, In the present study w e show that elongation factor 2 (EF2) mRNA is translationally regulate d in a growth-dependent manner in cells of hematopoietic origin, but n ot in any of three different non-hematopoietic cell lines studied, Hum an beta 1-tubulin mRNA is a new member of the family which contains al l the hallmarks of a typical TOP mRNA, yet its translation is refracto ry to growth arrest of any of the examined cell lines, Transfection ex periments indicate that the first 29 and 53 nucleotides of the mRNAs e ncoding EF2 and beta 1-tubulin, respectively, contain all the translat ional cis-regulatory elements sufficient for ubiquitously conferring g rowth-dependent translational control on a reporter mRNA, These; resul ts suggest that the distinct translational regulation of TOP mRNAs ref lects downstream sequences which can override the regulatory features of the 5' TOP in a cell type-specific manner. This notion is further s upported by the fact that mutations within the region immediately down stream of the 5' TOP of rpS16 mRNA confer onto the resulting transcrip ts growth-dependent translational control with a cell type specificity similar to that displayed by EF2 mRNA.