Feedback regulation of ribosomal protein gene expression in Escherichia coli: structural homology of ribosomal RNA and ribosomal protein MRNA.

Abstract

Certain ribosomal proteins (r proteins) in Escherichia coli, such as S4 -and S7, function as feedback repressors in the regulation of r-protein synthesis. These proteins inhibit the translation of their own mRNA. The repressor r proteins so far identified are also known to bind specifically to rRNA at an initial stage in ribosome assembly. We have found structural homology between the S7 binding region on 16S rRNA and a region of the mRNA where S7 acts as a translational repressor. Similarly, there is structural homology between one of the reported S4 binding regions on 16S rRNA and the mRNA target site for S4. The observed homology supports the concept that regulation by repressor r proteins is based on competition between rRNA and mRNA for these proteins and that the same structural features of the r proteins are used in their interactions with both rRNA and mRNA.In exponentially growing Escherichia coli cells, the rates of synthesis of most if not all ribosomal proteins (r proteins) are essentially identical to the rate of ribosome accumulation and coordinately regulated in response to environmental changes. A feedback model for translational regulation has been suggested to explain this balanced synthesis of r proteins (1), and there is experimental evidence that supports and refines this model (2-4). In this model, it is proposed that certain free r proteins act as feedback inhibitors of the translation of their own mRNAs and that, as long as the assembly of ribosomes removes r proteins, the corresponding mRNA escapes from the inhibition and continues to direct their synthesis. It has been shown in vitro, by using a protein synthesizing system that has various template DNAs carrying r-protein genes (2) and, in vivo, by examining the effect of overproduction of certain r proteins on the synthesis of other r proteins (3), that L1 (and not Lii) is the translational repressor that regulates the synthesis of both L11 and Li in the LIi operon (see Fig. 1). Similarly, S4 (2, 3), S8 (2), S7 (see below), L4 (4, 5), and L10 (6, 7; unpublished results) have been shown to be translational repressors involved in the regulation of the a, spc, str, S10, and 3 operons, respectively.Repressor r proteins probably interact with a specific region of polycistronic mRNA and cause their inhibitory effects indirectly on distal genes through a "polar effect." For example, the in vitro synthesis of Li from DNA templates that carry the Li gene but lack the promoter and an adjacent segment of the LIi gene is not inhibited by L1. This and other experiments have shown that the site of action of Li is localized in a regionThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 7084 of the mRNA that includes the beginning part of the Lii message (unpublished data). One plausible way to explain these observations and the balanced synthesis of Lii and Li is to assume that every r...

Undesired usage and the robust self-assembly of heterogeneous structures

“…Finally, it is intriguing to ask how the organization of operons-sets of bacterial genes whose expression is regulated together-is related to potential undesired complexes 51,52 . There is evidence for such connections between genome structure and the physics of protein complexes in other contexts 53,54 .…”

Regulation of lactate dehydrogenase synthesis in a ruminal bacterium, Streptococcus bovis.

“…However, LDH synthesis in S. bovis appeared to be enhanced by the increase in growth rate, which is also true for some enzymes in E. coli (Pease and Wolf, Jr., 1994). Several steps may affect gene expression which could be subject to growth control (e.g., the transcriptional, translational, and mRNA stability levels) (Nomura et al, 1980;Pease and Wolf, Jr., 1994;Resnekov et al, 1992). When S. bovis was grown in batch cultures, excess glucose was initially present and the growth rate was dependent upon the availability of glucose.…”

Translational feedback regulation of the gene for L35 in Escherichia coli requires binding of ribosomal protein L20 to two sites in its leader mRNA: A possible case of ribosomal RNA???messenger RNA molecular mimicry

“…In bacteria, the genes for ribosomal proteins (r-proteins) are clustered, and probably, as was shown to be the case in Escherichia coli, expressed as operons+ In this bacterium, the expression of r-proteins is often feedback regulated at the translational level by one of the operon products that binds to its own mRNA at a site called the operator+ Based on the apparent similarities between some of the r-protein translational operators in mRNAs and their binding sites on rRNA, Nomura et al+ (1980) proposed that the regulatory r-proteins recognize both sites similarly+ More importantly, it was hypothesized that a regulatory r-protein preferentially binds to its primary target, rRNA, and under conditions where rRNA sites are all occupied, it binds to the operator site on its own mRNA to block its own synthesis+ This notion of "mimicry" between two binding sites present on rRNA and mRNA has been convincingly demonstrated in the case of the L11-L1 operon (Nomura et al+, 1984;Zengel & Lindahl, 1994)+ In this operon, r-protein L1 directly down-regulates the expression of the gene encoding r-protein L11, and regulation is transmitted to the downstream L1 cistron by translational coupling+…”