Insights into the development of chemical probes for RNA

Morgan, Brittany S; Forte, Jordan E; Hargrove, Amanda E

While the potential benefits of selective RNA targeting are staggering, approaches toward chemical probe development must thoughtfully consider a number of variables, including transcript abundance and tissue-specific expression of the RNA target. By total mass and number of molecules, rRNA and tRNA account for greater than 90% of total cellular RNA in humans (96) , and thus mRNAs and other ncRNAs exist in a much lower abundance (1, 96, 97) . Even within these low abundance transcripts, copy numbers can vary widely within and across cell types with reports of mRNA levels spanning four orders of magnitude and some ncRNAs averaging less than one copy per cell (1, 97, 98) . A direct impact of RNA expression levels was recently reported, in which the authors proposed that ligand occupancy of the miRNA target was driven by the relative abundance of structurally similar RNA elements (16) . RNA with well-defined function and that are highly expressed thus represent low-hanging fruit within the field (6, 99) .