Yujing Li, Ph.D.
RNA interference (RNAi) is a well-conserved mechanism that uses small noncoding RNAs to silence gene expression post-transcriptionally. Gene regulation by RNA interference (RNAi) has been recognized as one of the major regulatory pathways in eukaryotic cells. The endogenous small RNAs can shape diverse cellular pathways, including chromosome architecture, development, growth control, apoptosis and stem cell maintenance. RNAi operates through two post-transcriptional mechanisms: targeted mRNA degradation (siRNA) and suppression of translation/degradation (miRNA). The RNAi mechanism has been co-opted by researchers and has achieved broad utility in gene-function analysis, drug-target discovery and validation, and therapeutic development. Although the major components in siRNA/miRNA pathway have been identified, little is known about the regulation of the RNAi pathway itself. Chemical biology is defined as the use of small molecules to probe gene function, pathways, and cellular phenotypes relevant to health and disease, and has been proven a powerful tool to dissect various biological pathways. To dissect cellular components modulating RNAi using chemical biology approach, we have developed a cell-based assay to monitor the activity of the RNAi pathway, and identified multiple small molecules that could modulate the activity of the RNAi pathway. Identification of these small molecules and study of their molecular actions would enable us to better understand the regulation of the RNAi pathway.