Figure 1.

RNA as a viable drug target. (A) The conventional binary approach to small molecule drugs is their molecular recognition of proteins. Among the ~20 000 proteins that comprise the proteome, only about 15% are in traditional “druggable” protein families. In turn, this only represents a fraction of the genome that is transcribed, leaving much of the transcriptome underexploited as therapeutic targets. (B) Noncoding genes relate to the complexity of the organism, as the relative number of coding bases remains similar, while the relative number of long noncoding RNAs (lncRNA) significantly increases, indicating that much of the intricacies of human biology and disease are represented among noncoding regions. (C) Due to the importance of coding and noncoding RNA to biology, small molecules interacting with RNA can act on the transcriptome, resulting in varied downstream effects. Importantly, validated activities for small molecules that target human RNA include: (i) changing gene expression by modulating the stability of mRNA by direct binding; (ii) affecting its noncoding RNA effectors; (iii) affecting the epitranscriptome; or (iv) influencing alternative splicing. Affecting the transcriptome with small molecule drugs can rescue disease by modulating the translation of beneficial or detrimental proteins.