MicroRNAs (miRNAs) are endogenous, non-coding RNAs which function as gene regulatory elements in eukaryotes. Previous research has shown that miR-71 significantly affects the longevity and stress resistance in C. elegans and that it functions through conserved pathways (1-6). In our current research we are extending these results by considering potential functions of miR-71 in nematode models of aging-associated neurodegenerative diseases such as Alzheimer's and Huntington's disease. Our findings show that miR-71 delays progressive paralysis in worms that express the human form of the Abeta1-42 amyloid, suggesting that miR-71 partially rescues worms from proteo-toxicity. We are currently examining the molecular mechanisms underlying miR-71's protective effect on proteo-toxicity. Since miR-71 functions, at least partially, through the IIS pathway, which mediates aging and stress resistance, we are examining if miR-71's function on proteo-toxic response is also mediated by the IIS pathway and to identify the molecular identity of the genes that respond to miR-71. Further, we have genetic evidence that links miR-71's role in proteotoxic response to the TGF-beta pathway. We are currently identifying the molecular identity of the genes that respond to miR-71. Since these pathways are highly conserved in nature it is hoped that insights uncovered by this research will help our understanding of disease of aging in humans.1. A. de Lencastre et al., MicroRNAs both promote and antagonize longevity in C. elegans. Curr. Biol. 20, 2159-2168 (2010).2. X. Zhang, R. Zabinsky, Y. Teng, M. Cui, M. Han, microRNAs play critical roles in the survival and recovery of Caenorhabditis elegans from starvation-induced L1 diapause. Proc. Natl. Acad. Sci. U.S.A. 108, 17997-18002 (2011).3. K. Boulias, H. R. Horvitz, The C. elegans MicroRNA
mir-71 Acts in Neurons to Promote Germline-Mediated Longevity through Regulation of DAF-16/FOXO. Cell Metabolism 15, 439-450 (2012).4. M. Lucanic et al., Age-related micro-RNA abundance in individual C. elegans. Aging (Albany NY) 5, 394-411 (2013).5. T. Smith-Vikos et al., MicroRNAs Mediate Dietary-Restriction-Induced Longevity through PHA-4/FOXA and SKN-1/Nrf Transcription Factors. Curr. Biol. 24, 2238-2246 (2014).6. C. Nehammer, A. Podolska, S. D. Mackowiak, K. Kagias, R. Pocock, Specific microRNAs Regulate Heat Stress Responses in Caenorhabditis elegans. Sci Rep 5, 8866 (2015).