Graded control of the trp operon through transcription attenuation. (a) The leader sequence of the trp mRNA. The transcript generated from the trp promoter includes a leader sequence at the 5′ end (containing four regulatory regions labeled 1 through 4). A portion of this sequence (sequence 1) is translated into the leader peptide, which has no known function other than to regulate the trp operon. (b) In the presence of tryptophan, the ribosome translates quickly through the Trp codons of sequence 1 and into sequence 2, allowing sequences 3 and 4 to associate to form a hairpin that stalls the RNA polymerase and terminates transcription. (c) In the absence of tryptophan, the ribosome stalls in sequence 1, allowing sequences 2 and 3 to associate. With sequence 3 unavailable to associate with sequence 4, the terminator structure is not formed and transcription can proceed. The amount of free tryptophan available for protein synthesis thus determines whether the trp operon is transcribed.