A new mechanism for “RNA memory”! 😱 Thrilled to share another crazy paper from the lab (can’t believe we posted 2 in 2 days!), summarizing >10 years of research: 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! 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. In this new work, an amazing collaboration with the Rink and Wurtzel labs, 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 (that are required in C. elegans). 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), making this particularly surprising. These are totally different animals. We find that ingestion of double-stranded RNA induces sequence-specific silencing that persists for months and survives repeated cycles of whole-body regeneration. 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…) Mechanistically, we find that the response transitions from a transient systemic dsRNA-triggered phase to a stable, cell-autonomous post-transcriptional “memory phase” maintained by antisense small RNAs. 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. RNAi inheritance without canonical RdRPs establishes planarians as a powerful system for studying RNA-based regulatory inheritance beyond C. elegans and raises the possibility that RNA-mediated inheritance may be more broadly conserved in animals, potentially even in mammals. Here’s a video of a planarian that is treated by RNAi against β-catenin and develops multiple heads instead of just one. This is one of the phenotypes that is inherited. Another phenotype is “loss of eyes” (which we show is not only inherited across multiple regeneration cycles, but can also be transmitted between animals in transplantation experiments). Amazing work led by first authors Prakash Cherian and Idit Aviram (co-supervised by Omri and me). Please read the preprint, the link is in the next tweet, and share!

Our🥶COOLNESS paper to date is finally published! Ice cold and lithium dramatically delay forgetting (extend memory) Why? read now in @NatureNeuro (as discussed first on the @hubermanlab podcast) rdcu.be/eVhn2

Antiviral reverse transcriptases reveal the evolutionary origin of telomerase

BIG ANNOUNCEMENT📣: I haven’t been this excited to be part of something new in 15 years… Thrilled to reveal the passion project I’ve been working on for the past year and a half!🙀🥳 It started from my frustration with the depressing effect that the current publishing system has on the well-being of myself, my team, and pretty much every scientist I know (maybe you’ve noticed from my stupid jokes… :) I was exhausted of dealing with the huge delays, reviewers that can be abusive, and how arbitrary it all is. Unfortunately, the most important factors are often WHO your reviewers are and who YOU are... It’s clear we need alternatives or at least ways to improve the situation. So, together with a really special and talented team we worked to develop this idea into “qed” a platform where you can get CONSTRUCTIVE feedback on your own work or CRITICALLY assess other people’s papers. It can be a real difference maker if many of you join us (thousands have tried it already, but today we release a NEW and much stronger version ;) Let’s harness qed to put the power back in the scientists’ hands, to do, to read & to publish science on our own terms. I’m dying for you to TRY IT, and it’s very simple - just drop a paper (the link to the website is in the replies👇) - it’s completely secure, private, and free, and you get results fast. Please show your support, SHARE, tell your friends, and let’s be the revolution 🫵!

Epigenetics is amazing