Oded Rechavi

Why is this figure hiden in the supplementary materials?

We are excited to be recruiting into 3 Associate Professorship's in @oxfordbiochemistry.bsky.social. Come join us as a colleague and benefit from our vibrant and multidisciplinary environment. Reach out to me if you have any questions. Please repost! (tinyurl.com/48deybuu) (tinyurl.com/4pdvjaft).

RNA really can do it all!

I am not sure. I believe GFP is technical and doesn't work partly because of autofluorescence. A more general barrier to stable transgenesis might be that they don't go through the bottleneck of a single cell, and I don't think anyone (as far as i know) succeed doing CRISPR.

Exactly! There might be many different feed forward mechanisms that do the trick, other than RdRPs

Indeed multiheaded worms don't eat well, so we could only follow them for a few generations. That's why we monitored also other phenotypes, like silencing of ovo-1, which leads to eye loss. Eyeless worms are ok, and we found that this phenotype persists for many months and many regeneration cycles.

Transgenerational epigenetic inheritance without RdRP...!

Lack of RdRP was one reason people argued epigenetic phenomena in nematodes (which do have RdRP) are fascinating but maybe not relevant to other animals (which don't have RdRP). But now....

BIOLOGY!

Thanks Leah!

Thrilled to finally see this work out! Congrats to everyone involved 🪱🧪✨

Please read the preprint (link below) and share!
www.biorxiv.org/content/10.6...

Amazing work led by first authors Prakash Cherian and Idit Aviram (co-supervised by Omri and me).

It also raises the possibility that RNA-mediated inheritance may be more broadly conserved in animals, potentially even in mammals.

RNAi inheritance without canonical RdRPs establishes planarians as a powerful system for studying RNA-based regulatory inheritance beyond C. elegans.

Using a new luminescence reporter (transgenesis is currently impossible in planarians), we show that silencing spreads along the targeted gene and identify a weird type of planarian small RNAs with untemplated polyA tails.

Mechanistically, the response transitions from a transient systemic dsRNA-triggered phase to a stable, cell-autonomous post-transcriptional “memory phase” maintained by antisense small RNAs.

Even more strikingly, RNAi can be transferred between animals, echoing James V. McConnell’s controversial “RNA memory” experiments from the 1970s (his lab was targeted by the Unabomber terrorist Ted Kaczynski, who sent McConnell a bomb. This and other controversies ended this line of experiments…)

We find that ingestion of double-stranded RNA induces sequence-specific silencing that persists for months and survives repeated cycles of whole-body regeneration.

You might say “they are both worms…” BUT planarians are evolutionarily very distant from C. elegans (flatworms vs roundworms, diverged more than 500 million years ago). These are totally different animals.

In this new work we show that planarians establish long-lasting and heritable small RNA–based gene regulatory states despite lacking canonical RNA-dependent RNA polymerases and nuclear RNAi machinery.

However, it’s still unclear whether RNAs are inherited across generations in other animals, largely because the RNA-dependent RNA polymerases that amplify heritable small RNAs and prevent their dilution in C. elegans are not conserved in mammals.

Work on transgenerational inheritance of small RNAs in the powerful model organism C. elegans changed how we think about what’s possible in inheritance and evolution, because it allows the most heretical thing: inheritance of parental responses to the environment!

A new mechanism for “RNA memory”! This time in Planaria! (Here's a video of a Planarian with mulitple heads, one of the heritable phenotypes we studied).

This work summarizes >10 years of research and is an amazing collaboration with the labs of Jochen Rink and Omri Wurtzel labs. Read thrad below👇

Thank you!!

One preprint 👇 is already alive, another🔥preprint is currently being screened by the good people at @openrxiv.bsky.social ❤️. Hopefully it’ll also be online today or tomorrow!

The parallel to the original sin I follow :)

Add last thing: of course we ran every iteration of this manuscript in @qedscience.bsky.social for feedback. We’re working on an option to open the qed reviews so I can share the comments with you on the platform. Coming soon!

Congrats to Itai Rieger, Yael Mor, Itamar Lev, and all the other authors on a superb job (this was many years in the making)

As always, the best thing about posting on @openrxiv.bsky.social is that we can get feedback from the community before the paper is published. Please send me or the other corresponding authors comments, we really appreciate it

Humanity is notorious for leaving problems for the next generations, but animals reveal the biology: C. elegans develop germline tumors if THEIR GRAND GRANDPARENTS’ cells fail to clear garbage from their body cavity… What the hell, you ask? Read our new preprint! 👇
www.biorxiv.org/content/10.6...