SsrA-mediated tagging and proteolysis of LacI and its role in the regulation of<i>lac</i>operon

Abo, Tatsuhiko; Inada, Toshifumi; Ogawa, Kazuko; Aiba, Hirofumi

doi:10.1093/emboj/19.14.3762

Cited by 126 publications

(165 citation statements)

References 35 publications

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“…In the regulation of several sugars, such as lactose (29), galactose (30), and arabinose (20), the main regulator is known to regulate its own activity in addition to transport and metabolism. This action of R on itself is the simplest addition to our two-loop motifs.…”

Section: Two-loop Motifs Arementioning

confidence: 99%

Combinatorics of feedback in cellular uptake and metabolism of small molecules

Krishna¹,

Semsey

Sneppen³

2007

Proc. Natl. Acad. Sci. U.S.A.

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We analyze the connection between structure and function for regulatory motifs associated with cellular uptake and usage of small molecules. Based on the boolean logic of the feedback we suggest four classes: the socialist, consumer, fashion, and collector motifs. We find that the socialist motif is good for homeostasis of a useful but potentially poisonous molecule, whereas the consumer motif is optimal for nutrition molecules. Accordingly, examples of these motifs are found in, respectively, the iron homeostasis system in various organisms and in the uptake of sugar molecules in bacteria. The remaining two motifs have no obvious analogs in small molecule regulation, but we illustrate their behavior using analogies to fashion and obesity. These extreme motifs could inspire construction of synthetic systems that exhibit bistable, history-dependent states, and homeostasis of flux (rather than concentration).homeostasis ͉ network motif ͉ regulation ͉ sugar uptake F eedback and biological regulation are two sides of the same coin, reflecting the need of the living cell to deal with changing environments, to generate cell to cell heterogeneity and to optimize cellular metabolism to a given external condition (1-6). The interplay between function and design of regulatory systems is a key issue in understanding cellular processes, and for engineering artificial biological circuits (7,8). In a few relatively simple biological circuits, like the genetic switch in phage lambda (9), the connection between the regulatory logic and its biological function has been partially clarified. For larger scale regulatory networks, it has also been suggested that feed-forward motifs are associated with particular functions (10). However, feedback loops are, in fact, the most common network motifs in cellular organization, especially when one considers the regulation of small molecules (11), ranging from minerals to nutrients required for proper cellular function. A large class of cellular response systems are designed to regulate the flux and concentration of these molecules by controlling, via two feedback loops, the transport and metabolism pathways. Typically, these two loops are connected by a common transcriptional regulator that senses the concentration of the small molecule. In fact, almost half the transcription factors in Escherichia coli are directly regulated by a small molecule (12, 13).Here we investigate the possible logical structures of such entangled loops involving small molecules and explicate, for these network motifs, a direct connection between structure and function of molecular regulation. There are four distinct logical structures for two entangled feedback loops, shown in Fig. 1. Inspired by their functional behavior we label the first two the socialist and the consumer motifs. The former balances the influx (transport) and outflux (metabolism) preventing large variations in the concentration of the small molecule. The latter, in contrast, responds by maximizing both influx and outflux.The other two logical ...

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Section: Two-loop Motifs Arementioning

confidence: 99%

Combinatorics of feedback in cellular uptake and metabolism of small molecules

Krishna¹,

Semsey

Sneppen³

2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Other phages also use SsrA for detecting host physiology: the immP22 hybrid phages do not grow on SsrA Ϫ strains (27,28,33). The E. coli LacI and LexA repressors, as well as the phage cI repressor (28,30) are targets of SsrA, suggesting that SsrA could be part of a general sensing mechanism.…”

Section: Mutations In Ssra Confer the Same Phenotype As Truncated Formentioning

confidence: 99%

“…Abo et al (30) recently reported that truncated LacI repressor forms appear in an SsrA Ϫ strain. They proposed a mechanism by which the binding of Lac repressor at the end of the lacI gene and DNA looping hinder RNA polymerase and, hence, ribosome progression.…”

Section: How Are Truncated Forms Of Mu Repressor Generated and Are Theymentioning

confidence: 99%

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The tRNA function of SsrA contributes to controlling repression of bacteriophage Mu prophage

Ranquet

Geiselmann

Toussaint

2001

Proc. Natl. Acad. Sci. U.S.A.

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The small regulatory RNA SsrA has both tRNA and mRNA activities. It charges alanine and interacts with stalled ribosomes, allowing for translation to resume on the SsrA mRNA moiety. Hence, unfinished peptides carry a short amino acid tag, which serves as a signal for degradation by energy-dependent proteases. In SsrAdefective Escherichia coli strains, thermoinducible mutants of the transposable bacteriophage Mu (Mucts) are no longer induced at high temperature. Here we show that truncated forms of the key regulator of Mu lysogeny, the repressor Repc, accumulate in the absence of SsrA. These forms resemble C-terminally truncated dominant Mu repressor mutants previously isolated from Mucts, which are no longer thermoinducible and bind operator DNA with a high affinity even at high temperature. Using various ssrA alleles, we demonstrate the importance of SsrA charging on the ribosome for controlling Mu prophage repression. Our results thus substantiate the previous observation that trans-translation is not the only function of the SsrA. The alternative function of SsrA appears to influence the stability of Mu lysogens by controlling the translation of the C-terminal domain of the repressor protein, which modulates the affinity of the protein for DNA and its susceptibility to proteolytic degradation.Mu repressor ͉ tmRNA ͉ truncated proteins ͉ lysis-lysogeny switch

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“…Proteolysis of tagged LacI transcriptional repressor in E. coli keeps the optimal concentration of repressor in the cells (17). trans-Translation and proteolysis of tagged substrates are required for correct timing of DNA replication in Caulobacter crescentus (18).…”

Section: Introductionmentioning

confidence: 99%

Structural aspects of trans‐translation

et al. 2010

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Summarytrans-Translation is a process which the bacterial cells apply to rescue the ribosomes that are arrested during the translation of damaged mRNA and to get rid of the mRNA and the product polypeptide. In the course of trans-translation, the mRNAlike domain of tmRNA replaces the nonstop messenger RNA bound to the ribosome. Although several structural elements of tmRNA and SmpB known to be essential for correct determination of resume codon, the molecular mechanism of trans-translation is not well understood. Computer modeling has been used to develop a model for the spatial organization of the tmRNA inside the ribosome at different stages of trans-translation leading to a proposal for the mechanism of the templateswitching process.

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SsrA-mediated tagging and proteolysis of LacI and its role in the regulation oflacoperon

Cited by 126 publications

References 35 publications

Combinatorics of feedback in cellular uptake and metabolism of small molecules

Combinatorics of feedback in cellular uptake and metabolism of small molecules

The tRNA function of SsrA contributes to controlling repression of bacteriophage Mu prophage

Structural aspects of trans‐translation

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