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 |
|---|---|
| Stephen Banse | Characterization of extracellular RNAi signaling molecules |
| Jeiwook Chae | function of the vertebrate SID-1 homologs during normal development |
| Deborah de Jong | Environmental RNAi and SID-1 interacting proteins |
| Andrea Hinas | Intercellular RNAi transport in C. elegans |
| Kyla Horn | Neurobiological significance of the mammalian sid-1 homolog SidT2" |
| Antony Jose | Export of RNA silencing signals from C. elegans tissues. |
| Yunsoo Kim | Determining the function of two genes in the pathway of systemic RNA interference |
| George Lu | Structure-function analysis of sid-1 mutants. |
| Nathan Nakatsuka | Phenotypic and genetic analysis of mammalian SID-1 homolog knock-out and knock-down mice. |
| Kenneth Pang | Role and significance of mammalian SID-1 homologs |
| Aidan Porter | Screening for components that regulate systemic RNAi in C. elegans |
| Daniel Schott | C. elegans as a model animal for virus infection |
| Joseph Shih | Intercellular dsRNA transport and mechanism of SID-1 function |
| Jessica Smith | Identifying factors required for the systemic spread of silencing initiated by endogenous RNAi. |
| Fei Song | In C. elegans, SID-1 serves a critical role in enabling the systemic spread of RNA interference. The goal of my research is to understand the role of mammalian SID-1 homologs through the development and analysis of SID-1 transgenic mice. |
| Jennifer Whangbo | Mechanisms that control the transport of dsRNA into and between cells in C. elegans |
| Eric Wu | Role of SID-1 in coordinating stress response in C. elegans |
| Jimmy Zhuang | Characterization of the enhancement of RNAi and the distinction between cell-autonomous versus transport-related RNAi effects. |