Figure 7–54 Post-transcriptional controls of gene expression. the final synthesis rate of a protein can, in principle, be controlled at any of the steps listed in capital letters. in addition, rnA splicing, rnA editing, and translation recoding can also alter the sequence of amino acids in a protein, making it possible for the cell to produce more than one protein variant from the same gene. Only a few of the steps depicted here are likely to be critical for the regulation of any one particular protein.
transcription Attenuation Causes the premature termination of Some rnA Molecules
It has long been known that the expression of some genes is inhibited by premature termination of transcription, a phenomenon called transcription attenuation. In some of these cases, the nascent RNA chain adopts a structure that causes it to interact with the RNA polymerase in such a way as to abort its transcription. When the gene product is required, regulatory proteins bind to the nascent RNA chain and remove the attenuation, allowing the transcription of a complete RNA molecule.
A well-studied example of transcription attenuation occurs during the life cycle of HIV, the human immunodeficiency virus that is the causative agent of acquired immune deficiency syndrome, or AIDS. Once the HIV genome has been integrated into the host genome, the viral DNA is transcribed by the cell’s RNA polymerase II (see Figure 5–62). However, this polymerase usually terminates transcription after synthesizing transcripts of several hundred nucleotides and therefore fails to efficiently transcribe the entire viral genome. When conditions for viral growth are optimal, a virus-encoded protein called Tat, which binds to a specific stem-loop structure in the nascent RNA that contains a “bulged base,” prevents this premature termination (see Figure 6–89). Once bound to this specific RNA structure (called TAR), Tat assembles several host-cell proteins that allow the RNA polymerase to continue transcribing. The normal role of at least some of these proteins is to prevent pausing and premature termination by RNA polymerase when it transcribes normal cell genes. Thus, a normal cell mechanism has apparently been highjacked by HIV to permit transcription of its genome to be controlled by a single viral protein.
riboswitches probably represent Ancient forms of Gene Control
In Chapter 6, we discussed the idea that, before modern cells arose on Earth, RNA played the role of both DNA and proteins, both storing hereditary information and catalyzing chemical reactions (see pp. 362–366). The discovery of riboswitches shows that RNA can also form control devices. Riboswitches are short sequences of RNA that change their conformation on binding small molecules, such as metabolites. Each riboswitch recognizes a specific small molecule and the resulting conformational change is used to regulate gene expression. Riboswitches are often located near the 5ʹ end of mRNAs, and they fold while the mRNA is being synthesized, blocking or permitting progress of the RNA polymerase according to whether the regulatory small molecule is bound (Figure 7–55).
Riboswitches are particularly common in bacteria, in which they sense key small metabolites in the cell and adjust gene expression accordingly. Perhaps their most remarkable feature is the high specificity and affinity with which each recognizes only the appropriate small molecule; in many cases, every chemical feature of the small molecule is read by the RNA (Figure 7–55C). Moreover, the binding affinities observed are as tight as those typically observed between small molecules and proteins.