Cell biology of RNA interference, intercellular RNA transport and epigenetic inheritance
RNA interference (RNAi), RNA-induced sequence-specific degradation of mRNA, has emerged as a major mechanism of gene regulation in most eukaryotes and has important implications in biomedical research and drug development. Extensive research has led to a relatively detailed understanding of this process in the short time since its discovery. However, a much less explored aspect of RNAi is the uptake and transport of RNAi silencing signals between cells and generations in animals. Intriguingly, recent studies suggest that this represents a new means of intercellular and intergenerational communication, which may be of importance for example during stressful conditions. In some organisms, such as the nematode Caenorhabditis elegans, RNAi uptake and spreading occurs with high efficiency. By taking advantage of the many molecular and genetic tools available for C. elegans, a number of proteins required for RNA transport has been discovered.
From our previous studies, we know that the SID-5 protein is required for cell-cell transport of RNAi silencing signals in C. elegans and that it localizes to late endosomes/multivesicular bodies (Hinas, Wright and Hunter, 2012). Using a membrane yeast-two-hybrid screen, we subsequently identified several putative SID-5 interacting proteins, for example the conserved membrane fusion SNARE protein SEC-22, which negatively regulates RNAi efficiency (Zhao, Holmgren and Hinas, 2017). Current research is focused on further analysis of the identified SID-5 interacting proteins and their roles in RNAi and RNA transport. Recently, this has brought our attention to the effects of stress on epigenetic inheritance of gene expression.
In addition to the role of SID-5 interacting proteins in RNAi, RNA transport and epigenetics, we are currently involved in two projects regarding the use of C. elegans as a model for parasitic worms and their resistance to anthelmintics. One of these projects is a collaboration with Dr. Eva Tydén at the Swedish University of Agricultural Sciences (SLU), supported by Formas, and the other is part of a research environment grant from the Swedish Research Council (Vetenskapsrådet). We also collaborate with other groups interested in using C. elegans as a model for their research questions.