What triggers transcription attenuation in the tryptophan (trp) operon?

Transcription Attenuation in the trp Operon

Transcription attenuation in the trp operon occurs when ribosomes follow immediately behind the polymerase (option d).

Mechanism of Transcription Attenuation

Transcription attenuation in the tryptophan (trp) operon is a sophisticated regulatory mechanism that controls gene expression based on tryptophan availability. The process involves several key components:

• TRAP Protein (trp RNA-binding Attenuation Protein): In Bacillus subtilis, when tryptophan levels are high, the TRAP protein binds to the 5' leader region of the nascent trp mRNA 1.

• Ribosome Position: The critical factor triggering attenuation is the position of ribosomes relative to RNA polymerase. When ribosomes follow closely behind the polymerase, they influence which RNA secondary structures can form 2.

• Leader Peptide Translation: The process depends on translation of a small leader peptide that contains tryptophan codons. The ribosome's position during this translation is communicated to the RNA polymerase transcribing the leader region 2.

How Attenuation Works

1. When tryptophan is abundant:

   • Ribosomes translate the leader peptide efficiently and follow closely behind RNA polymerase
   • This prevents formation of the antiterminator hairpin structure
   • The terminator hairpin forms instead, causing RNA polymerase to stop transcription
   • Result: Transcription terminates before reaching the structural genes

2. When tryptophan is limited:

   • Ribosomes stall at the tryptophan codons in the leader peptide
   • This creates a gap between the ribosome and RNA polymerase
   • The antiterminator structure forms instead of the terminator
   • Result: Transcription continues into the structural genes

Evidence Supporting Ribosome Position as the Trigger

Research has demonstrated that mutations affecting translation of the leader peptide directly impact attenuation:

• When the start codon (AUG) for the leader peptide is mutated to AUA, transcription termination at the attenuator increases 3-5 fold, showing that leader peptide translation is essential for proper regulation 2.

• Only starvation for amino acids that occur late in the leader peptide (positions 10-12) relieves transcription termination, confirming that ribosome positioning is the key factor 2.

• In B. subtilis, while the TRAP protein is involved, its function is to induce transcription termination when bound to the leader RNA - but the actual mechanism still depends on the relationship between ribosomes and RNA polymerase 3.

Important Distinctions

• Not option a: Completion of leader peptide synthesis alone doesn't trigger attenuation - it's the relative position of ribosomes during synthesis.

• Not option b: The trp repressor binding to the operator is part of repression control, which is a separate regulatory mechanism from attenuation 4.

• Not option c: While hairpin loop structures are involved in the process, they are the result of attenuation, not the trigger.

• Not option e: Polymerase stalling is not the trigger; rather, it's the ribosome's position relative to the polymerase that determines which RNA structures form.

The experimental evidence clearly shows that the relative positioning of ribosomes following RNA polymerase is the critical factor that triggers transcription attenuation in the trp operon.