Transcription attenuation

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 

If tryptophan is limiting, the ribosome stalls out over the tryptophan codons on the mRNA of the leader sequence. This leaves the mRNA free to form the 

2-3 antiterminator hairpin, which stops the 3-4 terminator sequence from forming, so that the RNA polymerase continues to transcribe the rest of the operon. Transcription is attenuated in several other operons dealing with amino acid synthesis. In these cases, there are always codons for the amino acid, which is the product of the pathway that acts in the same way as the tryptophan codons in this example. 

There are four principal control mechanisms for prokaryotic transcription-alternative O factors, enhancers, operons, and transcription attenuation. Alternative o factors can direct RNA polymerase to different promoters, altering the choice of RNA product. 

Enhancers and silencers are DNA sequences usually found upstream of promoters that stimulate or reduce transcription, respectively. These sequences bind to specific proteins called transcription factors. 

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Many Genes for Amino Acid Biosynthetic Enzymes Are Regulated by Transcription Attenuation... 

Yanofsky, C., Konan, K.V., Sarsero, J.P. (1996) Some novel transcription attenuation mechanisms used by bacteria. Biochimie... 

Transcription Attenuation How would transcription of the E. coli trp operon be affected by the following manipulations of the leader region of the trp mRNA ... 

Is transcription attenuation likely to be an important mechanism of transcriptional regulation in eukaryotic cells ... 

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

Overall, for the trp operon, repression via the trp repressor determines whether transcription will occur or not and attenuation then fine tunes transcription. Attenuation occurs in at least six other operons that encode enzymes for amino acid biosynthetic pathways. In some cases, such as the trp operon, both repression and attenuation operate to regulate expression. In contrast, for some other operons such as the his, thr and leu operons, transcription is regulated only by attenuation. 

Fig. I The biosynthetic pathway of L-threonine, and its regulation in E. coli. Dotted lines indicate feedback inhibition. Thick dotted lines indicate transcriptional attenuation regulation...

Figure 1 Generalized model for sensing regulatory effectors by nascent mRNA leader transcripts. Transcription attenuation mechanisms have been identified in which the nascent transcript interacts with a translating 70S ribosome, a protein, an RNA molecule or a small metabolite, (a) Binding of the effector molecule promotes transcription termination, (b) Binding of the effector molecule promotes transcription readthrough (antitermination). See text for details.

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... 

Gollnick P, Babitzke P. Transcription attenuation. Biochim. Biophys. Acta. 2002 1577 240-250. 

Henkin TM, Yanofsky C. Regulation by transcription attenuation in bacteria how RNA provides instructions for transcription ter-mination/antitermination decisions. Bioessays. 2002 24 700-707. 

Gish K, Yanofsky C. Evidence suggesting cis action by the TnaC leader peptide in regulating transcription attenuation in the tryptophanase operon of Escherichia coli. 1. Bacteriol. 1995 177 7245-7254. 

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. 

Sudershana S, Du H, Mahalanabis M, Babitzke P. A 5 RNA stem-loop participates in the transcription attenuation mechanism that controls expression of the Bacillus subtilis trpEDCFBA operon. J. Bacteriol. 1999 181 5742-5750. 

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. 

Brand S, Wagner EG. Antisense RNA-mediated transcriptional attenuation occurs faster than stable antisense/target RNA pairing ... 

Heidrich N, Brand S. Antisense RNA-mediated transcriptional attenuation in plasmid pIP501 the simultaneous interaction between 62. two complementary loop pairs is required for efficient inhibition... 

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