ABSTRACT

This chapter explores how small RNAs can regulate different cellular processes, using tRNAs, microRNAs, and CRISPR RNAs as examples. All of these mechanisms depend on the formation of the correct shapes for proteins for to act upon.

The concepts are extended to the regulation of flipon structures by small RNAs to program the readout of genetic information from the genome. Since each flipon is essentially a binary switch, and there are many in gene regulatory regions, you can select for those that change how the transcript from a gene is compiled to produce different RNA products. Combined with split genes and alternative splicing, the mechanism creates enormous variability in the proteins produced from your genome.

The idea has two important implications. First, you can regulate cell function by DNA shape without the direct readout of DNA sequence. Structure-specific proteins that recognize the alternative conformation can assemble proteins with specific functions at that genomic location. Second, you can regulate the ability of the flipon to change shape with sequence-specific RNAs. This strategy changes the way we view the regulation of gene expression. It also provides a mechanism by which to evolve much more rapidly than with proteins. Changing the sequence of an RNA is far easier than perfecting a sequence-specific DNA-binding protein.