Ronald Breaker’s recent review on riboswitches and translation control, published in Cold Spring Harbor Perspectives in Biology,, describes the fascinating mechanisms of RNA regulation of gene expression. Riboswitches are defined as RNA structures, typically found in the 5’ untranslated region (5’UTR) of mRNA, that sense and respond to small molecules, metabolites, or coenzymes to regulate transcription and translation. While he speculates that many riboswitch classes likely remain to be discovered, the article nicely highlights a number of riboswitch mechanisms that have been elucidated.
Direct translation control is discussed, involving a ligand-aptamer interaction that alters RNA structure in a way that either displays or occludes the ribosome binding site (RBS) of an mRNA. An example of this mechanism is a 5’UTR self-splicing riboswitch that, upon binding of an upstream aptamer to a cyclic RNA dinucleotide (c-di-GMP-II), triggers group I ribozyme splicing and yields an mRNA that can be properly translated. Conversely, the focus of the review then shifts towards the activity of ribozymes in indirect regulation of translation. Such mechanisms involve aptamers binding small molecules and forming structures that either promote or inhibit splicing of a pre-mRNA. Aptamer regulation of RNA splicing can be required for the processing of mature mRNA, cause aberrant splicing that results in non-functional products, or affect mRNA stability through removal of the 3’ polyadenylation sequence.
As this field of RNA biology progresses, Ronald Breaker indicates that there will be a need for new methods that can monitor RNA structures in real time across their folding pathways. This work will reinforce our understanding of how genes and complex biological processes are regulated in response to small ligand interactions with RNA and provide molecular sensors and switches for synthetic biology applications.
- Breaker, Ronald R. “Riboswitches and Translation Control.” Cold Spring Harbor perspectives in biology (2018). doi:10.1101/cshperspect.a032797