How do LINE family retrotransposons jump around? Can we reprogram retrotransposons? What does this have to do with Rum and Raisin? Answers here and below!

R2 is an exquisite LINE-like retrotransposon that inserts in ribosomal DNA repeats. Thomas Eickbush et al have done so much awesome work, showing that the R2 protein is INSANE: by itself, it finds a DNA target, cuts it, and reverse transcribes its own RNA right there and then.

We had a bunch of questions about R2, so solved its structure #CryoEM Q: How does R2 find its target? A: We found two sequence motifs, we call them the RUM and RASIN 🥃+🍇 RUM is bound by accessory DNA binding domains on R2.

When R2 binds the RUM, it unzips the RASIN, then cuts one strand of the RASIN. The cut strand is used as a primer for reverse transcription of the R2 RNA - so this is called TPRT (target-primed reverse transcription)

R2 is really specific for reverse transcribing its own RNA (i.e. its 5'UTR, ORF, 3'UTR) Q: What makes it so specific? A: A surprisingly small part of the 3'UTR: two hairpins and a linker. Only 40 nt!

Now it gets really fun: based on the structure, we can devise the ✨R2-tag✨ - 43 nt that you can attach to any RNA, and R2 will integrate it into the ribosomal DNA. (sorry, I ran out of movies)

ALSO R2 doesn't have to use the ribosomal DNA target, it can be retargeted: fused to Cas9, it can instead reverse transcribe at the Cas9 nick site. Maybe this could one day be really useful for gene therapy.

(Just kidding, one more movie) Thank you my lovely co-authors @FrangiehChris @zhangf and Rhi Macrae Also @bradyajohnston's #MolecularNodes Blender plugin is great. Everyone should use it. #b3d

the inevitable forgotten link to the actual paper!

You absolutely smashed it these animations are INCREDIBLE!! Very cool science also!