Nuclear processing of mRNA precursors in differentiating multicellular Dictyostelium discoideum aggregates is markedly slower than in growing amoebae. Synthesis of a protein can be regulated at many levels (9). During differentiation of Dictyostelium discoideum protein synthesis has been shown to be regulated at the levels of transcription, translation, and stability of the mRNA (22). We show here that the level of cytoplasmic mRNA in developing cells can also be regulated at the level of nuclear processing and transport to the cytoplasm.Differentiation of growing Dictyostelium amoebae is induced by amino acid starvation; an initial response to starvation is a preferential inhibition of translation of certain mRNAs (2). During and just after formation of multicellular aggregates, about 2,000 to 3,000 new species of mRNA appear on the polyribosomes (5). Induction of most of these mRNAs is at the transcriptional level (20,33). Many of these developmentally regulated RNAs are specifically labilized when the multicellular aggregates are disaggregated; the stability of many members of this class of mRNAs is specifically increased by high levels of extracellular cyclic AMP and possibly also by cell-cell contact (7,24,26).In growing cells processing of mRNA and rRNA is rapid; only a few minutes are required t Present address: Biologia Generale, 10126 Turin, Italy.for a newly synthesized mRNA or rRNA to be processed within the nucleus and exit into the cytoplasm (13, 23). There is no accumulation of nuclear precursor to rRNA, or of nuclear polyadenylated [poly(A)+] RNA. One of the predominant alterations in nucleic acid metabolism after induction of differentiation is a markedly reduced rate of nuclear RNA processing (17). Several nuclear pre-rRNAs are accumulated (4), and nuclear poly(A)+ RNA does not exit into the cytoplasm until 1 or 2 h after synthesis (14). Although we do not understand why the rate of processing, transport, or both, of nuclear premRNAs in multicellular aggregates is so slow, this system is an appropriate one in which to determine the limiting step in nuclear processing for individual mRNAs. We show here that in multicellular aggregates 50 to 100 min is required for most species of developmentally regulated mRNAs to be transported to the cytoplasm, whereas only 25 to 60 min is required for processing of most species of "common mRNAs," i.e., those synthesized during both growth and differentiation.One particular class of developmentally regulated mRNAs share sequences homologous to a set of repetitive DNA sequences (34). We show here that many of the poly(A)+ nuclear RNAs