Mellman, Katharine et al. (2019) International Worm Meeting "Mechanisms of RNA export from C. elegans tissues."

Mellman, Katharine, L'Etoile, Noelle

[International Worm Meeting, 2019]

The spread of RNA species in C. elegans is both an invaluable tool within the research community as well as a fascinating biological phenomenon in its own right. As a tool, RNAi has illuminated a wide-range of biological processes. Ongoing studies into endogenous RNA are revealing new mechanisms of gene regulation across tissues and generations. Much work has addressed the import of RNA species into various tissues. However, much work remains to elucidate the export of these RNA species. Here, using RNAi as a model, we explore mechanisms of RNA export. We seek to identify both druggable and biologically relevant points of regulation. Specifically, we investigate the role of autophagy pathway members in the dynamics of RNA signal spread. We demonstrate that autophagic mutants (atg-3, atg-7) demonstrate slowed silencing in target tissues.

Mellman, Katharine et al. (2017) International Worm Meeting "Identifying mechanisms of RNA export from C. elegans neurons."

L'Etoile, Noelle, Mellman, Katharine

[International Worm Meeting, 2017]

An organism's survival is rooted in its ability to sense and respond to stimuli. C. elegans is able to detect and interpret a variety of environmental cues, and is further able to integrate and disseminate this information to somatic and germline cells. Much of this communication is accomplished through canonical neuronal signaling. However, previous work in the field suggests this is not the only method. Mobile RNA signals, such as exogenous RNA interference (RNAi) and endogenous small interfering RNA (endo-siRNA) present an alternative mechanism by which neurons can communicate with the rest of the body. Both artificially induced RNAi and endo-siRNA generated in neurons are capable of spreading throughout the body, and enacting change on target cells. RNA signaling encompasses a multitude of pathways directed by a self-propagating species and initiated by events including external factors and responses to environmental stimuli. Endo-siRNAs generated in response to environmental changes exit from the site of production, frequently neurons, and spread to other cells to regulate gene expression. However, the mechanism of export along with potential points of regulation remains unknown. To monitor and manipulate the rate of export from neurons, we identified several genes whose expression is responsive to environmental changes (via endo-siRNA), as well as generating a construct expressing inducible, tissue-specific double stranded RNA against GFP. Using these targets and tool in in varied genetic backgrounds, environmental conditions, and drug treatments we seek to identify how this process is achieved and regulated.