Translational control of specific genes during differentiation of HL-60 cells

Eukaryotic gene expression can be regulated through selective translation o f specific mRNA species. Nevertheless, the limited number of known examples hampers the identification of common mechanisms that regulate translation of specific groups of genes in mammalian cells. We developed a method to id entify translationally regulated genes. This method was used to examine the regulation of protein synthesis in HL-60 cells undergoing monocytic differ entiation. A partial screening of cellular mRNAs identified five mRNAs whos e translation was specifically inhibited and five others that were activate d as was indicated by their mobilization onto polysomes, The specifically i nhibited mRNAs encoded ribosomal proteins, identified as members of the 5'- terminal oligopyrimidine tract mRNA family. Most of the activated transcrip ts represented uncharacterized genes. The most actively mobilized transcrip t (termed TA-40) was an untranslated 1.3-kilobase polyadenylated RNA with u nusual structural features, including two Alu-like elements. Following diff erentiation, a significant change in the cytoplasmic distribution of Alu-co ntaining mRNAs was observed, namely, the enhancement of Alu-containing mRNA s in the polysomes. Our findings support the notion that protein synthesis is regulated during differentiation of HL-60 cells by both global and gene- specific mechanisms and that Alu-like sequences within cytoplasmic mRNAs ar e involved in such specific regulation.