Systemic RNAi and intercellular RNA transport

The discovery of RNAi has generated tremendous excitement in basic research, where RNAi is an important tool, and in medicine, where dsRNAs are being developed as therapeutics to regulate disease causing genes and viruses. The last few years has seen significant progress in deciphering the intricacies of how introduction of dsRNA into cells leads to gene-specific mRNA degradation. Less well understood is how microRNAs (miRNAs) and other endogenous hairpin RNA genes regulate mRNA expression, stability, and translation. A second aspect of RNAi, the ability of the gene-specific signal to spread between cells, has been little studied, but its implications are equally as large, both as a means to introduce therapeutic dsRNA into cells as well as a new mechanism of intercellular gene regulation.

Our discovery and characterization of C. elegans genes essential for the spreading of the RNAi signal has provided a mechanistic basis for understanding how gene-specific information is communicated between cells and the means to manipulate this new form of intercellular gene regulation. Current research efforts in the lab are directed at understanding how dsRNA transits the SID-1 dsRNA channel, investigating the function of vertebrate SID-1 homologs, determining how dsRNA is exported from and transported between cells, cloning and characterizing the other components identified in the original screen, and screening for additional genes involved in transporting dsRNA between cells.

Participating Lab Members:

Name Research
Jeiwook Chaefunction of the vertebrate SID-1 homologs during normal development
Deborah de JongLooking for protein interactions in systemic RNAi
Antony JoseUnderstanding the molecular machinery that transports RNAi between cells
Daniel SchottC. elegans as a model animal for virus infection
Joseph ShihIntercellular dsRNA transport and mechanism of SID-1 function
Jessica SmithIdentifying factors required for the systemic spread of silencing initiated by endogenous RNAi.