Introduction to Noncoding RNA

Key concept
RNA can function as a regulator by forming a region of secondary structure (either inter- or intramolecular) that can control gene expression.
The basic principle of gene regulation is that expression (transcription) is controlled by a regulator that interacts with a specific sequence or structure in DNA or mRNA at some stage prior to the synthesis of protein. The stage of expression that is controlled can be transcription when the target for regulation is DNA, or it can be at translation when the target for regulation is RNA. Control during transcription can be at initiation, elongation, or termination. The regulator can be a protein or an RNA. “Controlled” can mean that the regulator turns off (represses) or turns on (activates) the target. Expression of many genes can be coordinately controlled by a single regulator gene on the principle that each target contains a copy of the sequence or structure that the regulator recognizes. Regulators may themselves be regulated, most typically in response to small molecules whose supply responds to environmental conditions. Regulators may be controlled by other regulators to make complex circuits or networks.

Many protein regulators work on the principle of allosteric changes. The protein has two binding sites—one for a nucleic acid target, the other for a small molecule. Binding of the small molecule to its site changes the conformation in such a way as to alter the affinity of the other site for the nucleic acid. The way in which this happens is known in detail for the lac repressor in Escherichia coli. Protein regulators are often multimeric, with a symmetrical organization that allows two subunits to contact a palindromic or repeated target on DNA. This can generate cooperative binding effects that create a more sensitive response to regulation.

Regulation via RNA uses changes in secondary structure base pairing as the guiding principle. The ability of an RNA to shift between different conformations with regulatory consequences is the nucleic acid’s alternative to the allosteric changes of protein conformation. The changes in structure may result from either intramolecular or intermolecular interactions.
It was once thought that RNA was merely structural: mRNA carried the blueprint for the synthesis of a protein, rRNA was the structural component of the ribosome, and tRNA shuttled amino acids to the ribosome. It is now clear that there is a vast RNA world where RNAs have numerous functions, where mRNA can regulate its own translation (see the chapter titled The Operon), where rRNA catalyzes peptide bond formation , and where tRNAs participate in the mechanism of fidelity of translation .

The RNA world extends far beyond the three major RNA types—mRNA, rRNA, and tRNA—to include dozens of different RNAs. These RNAs can function as guide RNAs or as splicing cofactors. In addition, a large and very heterogeneous class of RNAs with known and suspected regulatory functions is described here and in the chapter titled Regulatory RNA. However, all the mysteries in this new RNA world have certainly not been resolved.