Use RNase P Multiloop Sequences to Create "Cross" Designs

Based on our energy model, the 4-branched multiloop with zero unpaired bases seems like a very strained, unstable beast. Instead of blindly stabbing at solutions, maybe we can take a hint from a few billion years of evolution.

Prokaryotic forms of RNase P, a well-studied ribozyme, contains this structural element. You can see it here in this bacterial sequence. Perhaps we could use RNase P sequences as guides for our own designs.

You could browse the RNase P Database or try this search in RNA STRAND. If you use RNA STRAND, try to view the structure from the original source, because its secondary structure drawings are small and hard to see.

EDIT: Okay, having tried this I will say i’ve had very little success finding an RNase P multiloop that is actually predicted to fold correctly in EteRNA. I’ve tried literally dozens of sequences, and each one fails. Obviously, Nature is wrong :stuck_out_tongue:

One thing that I have notices is that both EteRNA players and evolution seem to favor the two adjacent, identically oriented GC pairs when an internal loop (be it an FMN binding site or other loop) occurs very close to the multiloop. Weird.