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RNA-Mediated Inheritance of Acquired Traits (TransgenerationalRNA)
Date du début: 1 févr. 2014, Date de fin: 31 janv. 2019 PROJET  TERMINÉ 

Inheritance of acquired traits is a topic of long-standing interest and controversy. While some of the classic Lamarckian ideas have been dismissed, more recent observations suggest that certain characteristics acquired by an animal during its lifetime might be transmitted to the next generations. Recently I described, for the first time in animals, a biological context in which acquired traits are inherited via small RNA molecules, which ignore the boundary between the soma and the germ line (“The Weizmann Barrier”). Specifically, I showed that the nematode C.elegans inherit an acquired trait, antiviral resistance, through transgenerational transmission of antiviral small RNAs (viRNAs), which mediate RNA interference (RNAi) (Cell, 2011). viRNAs, which protect the worm from viral propagation, pass down to many ensuing generations in a non-Mendelian manner, in the absence of their DNA template, and thus defend RNAi-deficient progeny from viral propagation. Here I suggest defining the rules that govern RNA-mediated transgenerational inheritance of acquired traits and exploring its contribution for the genetics of complex traits. My first efforts will be directed towards elucidating the mechanism behind transgenerational transmission of small RNAs; I established a well-defined system for monitoring transgenerational silencing that should allow unveiling of its genetic and biochemical basis. Second, I will examine whether responses to relevant environmental stresses carry on to the next generations so that the progeny is better prepared to cope with similar conditions. Lastly, I will explore whether sensing of environmental cues by the nervous system drives small RNA biogenesis, which transfer transgenerationally and mediate inheritance of neuronally-encoded traits. While the idea that RNA encodes for “Inherited Memory” sounds heretic at first, my preliminary efforts suggest that inherited small RNAs may indeed transmit information about ancestral acquired experiences.