Escherichia coli ribosomal protein LI (0.5 gM) was found to inhibit the synthesis of both proteins of the LII operon, LII and LI, but not the synthesis of other proteins directed by Xrifd18 DNA. Similarly, S4 (I MM) selectively inhibited the synthesis of three proteins of the a operon, S13, Sii, and S4, directed by Xspcl DNA or a restriction enzyme fragment obtained from this DNA. S8 (3.6 gM) also showed preferential inhibitory effects on the synthesis of some proteins encoded in the spc operon, L24 and L5 (and probably S14 and S8), directed by Xspcl DNA or a restriction enzyme fragment carrying the genes for these proteins. The inhibitory effect of LI was observed only with LI and not with other proteins examined, including S4 and S8. Similarly, the effect of S4 was not observed with LI or S8, and that of S8 was not seen with LI or S4. Inhibition was shown to take place at the level of translation rather than transcription. Thus, at least some ribosomal proteins (LI S4, and S8) have the ability to cause selective translational inhibition of the synthesis of certain ribosomal proteins whose genes are in the same operon as their own. These results support the hypothesis that certain free ribosomal proteins not assembled into ribosomes act as "autogenous" feedback inhibitors to regulate the synthesis of ribosomal proteins.In exponentially growing Escherichia coli cells, synthesis rates of all ribosomal proteins (r-proteins) (except L7/L12) appear to be identical and coordinately regulatedin response to environmental conditions (for reviews, see refs. 1-3). Despite extensive studies on this-subject, molecular mechanisms involved in the regulation have remained unknown. We previously examined gene dosage effects on the synthesis of r-proteins encoded by the genes in the spc region (72 min) of the E. coli chromosome (4). It was found that the rates of transcription of the r-protein genes increase in proportion to the increase in gene dosage, but that the rates of r-protein synthesis do not increase relative to the synthesis rates of other r-proteins whose genes exist outside the spc region in a single copy per genome. From these experimental results we suggested that free r-proteins inhibit the translation of their own IiiRNA and that, as long as the assembly of ribosomes removes r-proteins, the corresponding mRNA escapes this feedback inhibition. We have tested this hypothesis by using an in vitro protein-synthesizing system with various template DNA molecules carrying r-protein genes. We have found that some r-proteins (S4, S8, and LI) selectively inhibit the synthesis of certain r-proteins whose genes are in the same operon as their own and that this "autogenous" inhibition is, in fact, at the level of the translation of mRNA rather than at the level of transcription. (5, 6). Fig. 1 shows the structures of the transducing phages. The 10% and 5% EcoRI fragments of Xfus3 were obtained from pNO1001 (14) and hybrid phage Ch3S450i (15), respectively.Ribosomal Proteins. The proteins were purified and stored in ...