Transcription Attenuation in Prokaryotes

Transcriptional attenuation is the early termination of transcription to prevent downstream gene expression. This is one of several strategies that bacteria use to regulate the synthesis of biomolecules according to their metabolic needs.

Transcriptional attenuation was first identified in E. coli at the trp operon. The operon contains a promoter and operator as well as five genes, trp A through E, which code for enzymes required for tryptophan synthesis. 

Before the first gene trp E, the trp operon has a leader sequence which encodes mRNA with four distinct segments, numbered 1 through 4. 

A transcription anti-terminator forms when segment 3 folds into a hairpin structure with segment 2. Alternatively, a transcription terminator occurs when segment 3 forms a hairpin structure with segment 4, allowing segment 2 to form a hairpin with segment 1 instead.  

In bacteria, transcription and translation can occur simultaneously. As soon as the 5' end of the messenger RNA is synthesized by RNA polymerase, a ribosome can bind and begin protein synthesis.

Segment 1 of the trp operon contains two tryptophan codons. When the ribosome encounters these codons, and high levels of tryptophan are present, tryptophanyl-tRNA, which is tRNA loaded with tryptophan, will quickly bind to the codons allowing the ribosome to continue moving forward.

When the ribosome reaches segment 2, this segment will not be available to bind to segment 3. Segment 3 will then form the terminator hairpin with segment 4.

This terminator causes RNA polymerase to detach from the DNA template and stop synthesizing the growing mRNA. This ensures that the genes needed for tryptophan synthesis are not transcribed when tryptophan is readily available.

However, if tryptophan levels are low, there will not be enough tryptophanyl-tRNA to bind to the codons in segment 1. This will result in the ribosome stalling at these codons.

Now segment 2 will form the anti-terminator hairpin with segment 3, and the terminator hairpin cannot form between segments 3 and 4.

The absence of the terminator allows RNA polymerase to continue its transcription of the trp operon.