According to epigenetics -- the study of inheritable changes in gene expression not directly coded in our DNA -- our life experiences may be passed on to our children and our children's children. Studies on survivors of traumatic events have suggested that exposure to stress may indeed have lasting effects on subsequent generations. But how exactly are these genetic "memories" passed on?
A new Tel Aviv University study pinpoints the precise mechanism that turns the inheritance of environmental influences "on" and "off." The research, published last week in Cell and led by Dr. Oded Rechavi and his group from TAU's Faculty of Life Sciences and Sagol School of Neuroscience, reveals the rules that dictate which epigenetic responses will be inherited, and for how long.
"Until now, it has been assumed that a passive dilution or decay governs the inheritance of epigenetic responses," Dr. Rechavi said. "But we showed that there is an active process that regulates epigenetic inheritance down through generations."
Highlights
•New RNAi episodes extend the duration of heritable epigenetic effects
•Amplification of heritable exo-siRNAs occurs at the expense of endo-siRNAs
•A feedback between siRNAs and RNAi genes determines heritable silencing duration
•Modified transgenerational epigenetic kinetics (MOTEK) mutants are identified
Summary
In C. elegans, small RNAs enable transmission of epigenetic responses across multiple generations. While RNAi inheritance mechanisms that enable “memorization” of ancestral responses are being elucidated, the mechanisms that determine the duration of inherited silencing and the ability to forget the inherited epigenetic effects are not known. We now show that exposure to dsRNA activates a feedback loop whereby gene-specific RNAi responses dictate the transgenerational duration of RNAi responses mounted against unrelated genes, elicited separately in previous generations. RNA-sequencing analysis reveals that, aside from silencing of genes with complementary sequences, dsRNA-induced RNAi affects the production of heritable endogenous small RNAs, which regulate the expression of RNAi factors. Manipulating genes in this feedback pathway changes the duration of heritable silencing. Such active control of transgenerational effects could be adaptive, since ancestral responses would be detrimental if the environments of the progeny and the ancestors were different.
Passing stress from one generation to the next
Researchers have been preoccupied with how the effects of stress, trauma, and other environmental exposures are passed from one generation to the next for years. Small RNA molecules -- short sequences of RNA that regulate the expression of genes -- are among the key factors involved in mediating this kind of inheritance. Dr. Rechavi and his team had previously identified a "small RNA inheritance" mechanism through which RNA molecules produced a response to the needs of specific cells and how they were regulated between generations.
Cell - A Tunable Mechanism Determines the Duration of the Transgenerational Small RNA Inheritance in C. elegans
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Reposted via Next Big Future
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