Concepts Summary

• Gene expression can be controlled at different levels, including the alteration of DNA or chromatin structure, transcription, mRNA processing, RNA stability, translation, and posttranslational modification. Much of gene regulation is through the action of regulatory proteins binding to specific sequences in DNA.
• Genes in bacterial cells are typically clustered into operons—groups of functionally related structural genes and the sequences that control their transcription. Structural genes in an operon are transcribed together as a single mRNA molecule.
• In negative control, a repressor protein binds to DNA and inhibits transcription. In positive control, an activator protein binds to DNA and stimulates transcription. In inducible operons, transcription is normally off and must be turned on; in repressible operons, transcription is normally on and must be turned off.
• The lac operon of E. coli is a negative inducible operon. In the absence of lactose, a repressor binds to the operator and prevents the transcription of genes that encode β-galactosidase, permease, and transacetylase. When lactose is present, some of it is converted into allolactose, which binds to the repressor and makes it inactive, allowing the structural genes to be transcribed.
• Positive control in the lac and other operons is through catabolite repression. When complexed with cyclic AMP, the catabolite activator protein binds to a site in or near the promoter and stimulates the transcription of the structural genes. Levels of cAMP are inversely correlated with glucose; so low levels of glucose stimulate transcription and high levels inhibit transcription.
• The trp operon of E. coli is a negative repressible operon that controls the biosynthesis of tryptophan.
• Attenuation causes premature termination of transcription. It takes place through the close coupling of transcription and translation and depends on the secondary structure of the 5′ UTR sequence.
• Antisense RNAs are complementary to sequences in mRNA and may inhibit translation by binding to these sequences, thereby preventing the attachment or progress of the ribosome.
• When bound by a regulatory molecule, riboswitches in mRNA molecles induce changes in the secondary structure of the mRNA, which affects gene expression. Some mRNAs possess ribozyme sequences that induce self-cleavage and degradation when bound by a regulatory molecule.