Transcription attenuation control

Du H, Yakhnin AV, Dharmaraj S, Babitzke P. trp RNA-binding attenuation protein-5 stem-loop RNA interaction is required for proper transcription attenuation control of the Bacillus subtilis trpEDCFBA operon. J. Bacteriol. 2000 182 1819-1827. 

The rate of TRAP binding to RNA is crucial for transcription attenuation control of the B. subtilis trp operon. J. Mol. Biol. 2007 370 925-938. 52. 

Kwak, J-H., Choi, E-C., and Weisblum, B. (1991). Transcriptional attenuation control of ermK, a macroUde-lincosamide-streptogramin B resistance determinant from Bacillus licheniformis. J. Bacterial. 173,4725 735. 

Transcription attenuation controls transcription after it has begun by adjusting the level of transcription based on the quantity of a related metabolite. For example, in the trp operon, the level of tryptophan affects the transcription of the genes that produce the enzymes that make tryptophan. 

Figure 1-5-3. Attenuation Control of Transcription in the Histidine Operon...

Yanofsky, C., Operon-specific control by transcription attenuation. Trends Genet. 3 356-360, 1987. 

TrpR, which is a DNA binding repressor protein, regulates transcription initiation of the E. coli trpEDCBA operon. Under tryptophan limiting conditions, TrpR represses transcription initiation, whereas repression is relieved in the presence of excess tryptophan. Once transcription initiates the elongating transcription complex is subject to control by transcription attenuation (reviewed in References 5 and 6). The leader transcript can form three RNA secondary structures that are referred to as the pause hairpin, the antiterminator structure, and an intrinsic terminator hairpin. Because the antiterminator shares nucleotides in common with the terminator, their formation is mutually exclusive. The pause hairpin has two additional roles in this transcription attenuation mechanism it serves as an anti-antiterminator stmc-ture that prevents antiterminator formation, and it codes for a leader peptide. A model of the E. coli trp operon transcription attenuation mechanism is presented in Fig. 2a. 

The most recently identified class of transcription attenuation mechanism involves direct sensing of the effector molecule by the nascent transcript (52-54). These RNA sensors control metabolically diverse pathways. As for the other attenuation and antitermination mechaiusms discussed thus far, recognition of the particular effector molecule occurs with the appropriate affinity and high specificity required for precise control of gene expression. 

The discovery of transcription attenuation over 30 years ago led to the realization that mRNAs serve a purpose beyond simply functioning as a conduit of information from DNA to protein. Indeed, the discovery of transcription attenuation established for the first time that RNA structure can modulate gene expression. It is now abundantly clear that expression of many genes is controlled by several different mechanisms after transcription... 

Babitzke P. Regulation of transcription attenuation and translation initiation by allosteric control of an RNA-binding protein the Bacillus subtilis TRAP protein. Curr. Opin. Microbiol. 2004 7 132-139. 

Attenuation Controls Transcriptional Elongation of trp Polycistronic mRNA... 

Taken together, the combined effect of Trp repressor-mediated transcriptional repression, and TRP-tRNATrp sensitive transcriptional attenuation provides a highly sensitive mechanism to control utilization of the tryptophan biosynthetic pathway. 

Attentuation - Further insight into termination mechanisms has come from an extensively studied regulatory mechanism called attenuation (Figure 26.33, Figure 26.36). Attenuation controls the rate of transcription of certain operons by terminating the synthesis of a nascent transcript before RNA polymerase has reached the structural genes. 

In prokaryotes, transcription is controlled in four principal ways—alternative O factors, enhancers, operons, and transcription attenuation. They will be discussed in turn. 

In addition to repression, the trp operon is regulated by transcription attenuation. This control mechanism works by altering transcription after it has begun via transcription termination or pausing. Prokaryotes have no separation... 

Elongation is controlled in several ways. There are sequences called pause sites, where the RNA polymerase hesitates. This is very similar to the transcription attenuation we saw with prokaryotes. Elongation can also be aborted, leading... 

Frequency of transcription is controlled by the promoter sequence. Additional sequences upstream can also be involved in regulating prokaryotic transcription. These sequences are called enhancers or silencers, and they stimulate or inhibit transcription, respectively. Proteins called transcription factors can bind to these enhancer or silencer elements. Many prokaryotic genes that produce proteins that are part of a pathway are controlled in groups called operons, and expression of some genes is controlled by transcription attenuation. 

In E. coli, at least three distinct transcription termination systems are known to operate (a) attenuation controls in some amino acid operons, (b) hairpin... 

One mechanism of transcriptional control in prokaryotes, especially of several operons controlling the biosynthesis of amino acids, is attenuation. 

Schematic diagram of the repressor control of trp operon expression. The trp promoter (P) and trp operator (O) regions overlap. The trp aporepressor is encoded by a distantly located trpR gene. L-Tryptophan binding converts the aporepressor to the repressor that binds at the operator locus. This complex prevents the formation of the polymerase-promoter complex and transcription of the operon that begins in the leader region (trpL). Only a fraction of the transcripts extends beyond the attenuator locus in the leader region. The regulation of this fraction is discussed in the text.

This attenuator mechanism of control is amazingly simple because it requires no proteins other than those normally used for transcription and translation. One might expect such a simple and effective mechanism to be used repeatedly for other operons involved in amino acid biosynthesis. Indeed, for several other amino acid biosynthetic pathways in E. coli for which tRNA charging is involved in regulation, attenuator mechanisms have been found. 

The trp operon has a control locus called an attenuator about 150 bases after the transcription initiation site. The attenuator is regulated by the level of charged tryptophan tRNA, so that between 10% and 90% of the elongating RNA polymerases transcribe through this site to the end of the operon. Low levels of trp tRNA encourage transcription through the attenuator. 

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