In an Escherichia coli strain lysogenic for Xspc2 transducing phage, an extra copy of ribosomal protein (r-protein) genes in the spc and a operons are carried on the phage chromosome. Expression of genes in the spc operon in this merodiploid strain was compared with that in a control "haploid" strain carrying XtrkA phage. It was found that the synthesis rate of spc mRNA, relative to other reference mRNA in the merodiploid strain, is about 2-fold higher than that in the control strain; yet, no dosage effect was observed in the synthesis rate of r-proteins in the spc or a operon. The spc mRNA was found to be more rapidly degraded in the merodiploid strain than in the control strain, and its steady-state amount, relative to reference mRNA, was only slightly higher in the merodiploid strain than in the control strain. Thus, E. coli cells have the ability to regulate the rate of r-protein synthesis regardless of the rate of transcription of r-protein genes, presumably by inactivation of the mRNA followed by its degradation. A model is proposed which involves selective inactivation of r-protein mRNA by a feedback mechanism. The model can explain coordinated synthesis of r-proteins and other observations related to selective expression of certain alleles in diploid strains.Ribosomes from Escherichia coli contain approximately 50 proteins. All of these proteins, with the exception of L7/L12, exist in a single copy per ribosome. In exponentially growing cells, there appears to be neither a significant pool of free ribosomal proteins (r-proteins) nor significant degradation of newly synthesized r-proteins. Therefore, all the r-proteins are apparently synthesized coordinately and stoichiometrically (for a review, see ref. 1). How this remarkable regulation is achieved is not known.In this paper, we report the results of experiments that show that E. coli cells have the ability to regulate the rate of r-protein synthesis regardless of the rate of transcription of r-protein genes. We then describe a new model which involves selective inactivation of r-protein mRNA by a feedback mechanism and discuss various available experimental observations. EXPERIMENTAL PROCEDURES Two E. coli K-12 strains were used. Both are lysogenic derivatives of strain N01230 (trkA401, kdpABC5, spCr, strr, fusr). One (NO1275) carries XtrkA transducing phage and XcI857S7 helper phage. The other (NO1328) carries Xspc2 transducing phage and the same helper phage. These strains and phages have been described (2, 3). All other experimental procedures are described in the figure and table legends. RESULTSWe initially asked whether an increase in the number of gene copies leads to an increase in the synthesis rate of corresponding r-proteins or if E. coli cells have the ability to regulate the synthesis rate regardless of gene copy numbers. The Xspc2 transducing phage carries 14 r-protein genes together with their promoters and 9 additional r-protein genes without their bacterial promoters (3, 4). The former 14 genes are organized into two operons ("...

Using ColE1-TnA hybrid plasmid RSF2124 as the cloning vector, we constructed a hybrid plasmid, pNO1001, which carried seven ribosomal protein (rprotein) genes in the spc operon together with their promoter. The plasmid also carried three r-protein genes which precede the spc operon, but did not carry the bacterial promoter for these genes. Expression of r-protein genes carried by pNO1001 was studied by measuring messenger ribonucleic acid and r-protein synthesis in cells carrying the plasmid. It was found that the messenger ribonucleic acid for all the promoter-distal r-protein genes was synthesized in large excess relative to messenger ribonucleic acid from other chromosomal r-protein genes which are not carried by the plasmid. However, only the two promoter-proximal r-proteins, L14 and L24, were markedly overproduced. The absence of large gene dosage effects on the synthesis of other distal proteins appeared to be due, at least in part, to preferential inactivation and/or degradation of the distal message which codes for these proteins; in addition, some preferential inhibition of translation of the distal message might also have been involved. Overproduced