Thread by @OdedRechavi

🔥🔥 New Pre-Print! 🔥🔥 We discovered that stress re-sets transgenerational small RNA inheritance in C.elegans. Read how worms change their epigenetic plans when they no longer fit their environment. A thread (1/13)👇 #molecularmemories
biorxiv.org/content/10.110…

First, huge congrats to @LeahHouri, @GuyTeichman and Hila Gingold!! It’s a pleasure to see lab members work so well in a team. (2/13)👇

Some background: In C.elegans nematodes, transgenerational RNAi typically lasts for 3-5 generations. This was shown by Rosa M. Alcazar et al. (Andrew Fire’s lab) many years ago (3/13)👇

We’ve shown a few years ago that an active feedback-based mechanism determines the number of generations that RNAi would last (Houri-Zeevi et al. Cell 2016), and found mutants where RNAi lasts much longer (Lev et al. Current Biology 2017). (4/13)👇

We found that repetitive activation of the RNAi system can *extend* the duration of heritable RNAi, but until now it was unknown whether any outside cue could *terminate* small RNA inheritance. This is what we show in this manuscript (keep reading) (5/13)👇

We found that if we stress progeny of RNAi-treated ancestors using different stresses (heat shock, starvation, or high salt) it re-sets the heritable silencing. They stop inheriting RNAi (6/13)👇

There’s a critical period when stress-induced resetting works: at the F1 generation. If you stress the F2s it’s already too late, they still inherit the response just like un-stressed progeny.
(7/13)👇

Would any change lead to re-setting of heritable RNAi, or does it have to be a stressful change? We find it has to be stressful. “Improving” the worms’ situation doesn’t lead to re-setting. (8/13)👇

We zoomed in and by examining many mutants, defective in different stress response genes, we found that resetting of heritable RNAi is orchestrated by MAPK pathway factors, and the transcription factor SKN-1 (9/13)👇

Further, we discovered that the MET-2 methyltransferase is required for execution of stress-induced resetting. (10/13)👇

In addition to re-setting of RNAi inheritance, we found that stress leads to a
genome-wide reduction in heritable small RNA levels & characterized which small RNA species are changing, and what’s special about each type of stress. (11/13)👇

We hypothesize that stress-induced resetting of small RNA inheritance could
protect from run-on of environment-irrelevant heritable gene regulation (12/13)👇

There’s a lot more in the paper, so go read it!!(13/13)
biorxiv.org/content/10.110…