Rachael Kretsch has published an astonishing new preprint paper titled Naturally ornate RNA-only complexes revealed by cryo-EM where she reveals the 3D structure of three large RNA-only molecules. I’m blown away by what she found. All three are much more ordered and symmetrical than I’ve seen in other RNA structures.
I’ll present all three individually for players to view and perhaps use for inspiration in our current 240mer design lab project.
The Ornate Large Extremophilic (OLE) RNA consists of two identical pieces of RNA that connect at three sites.
Our OLE dimer map shows that it is organized as a series of parallel A-form helices, like a bundle of pipes. The exterior ends of these pipes from each chain are interconnected into a five-way junction…
An unusual but highly conserved symmetric interaction comprised of four A-A base pairs between two chains (L4, Fig. 1D), intermolecular base-pairing and stacking interactions connecting L5, L6, and L7 (Fig. 1E), and a kissing loop (L9.3, Fig. 1F) ‘weld’ the pipes together in the middle of the complex. Hereafter we denote these intermolecular interactions ‘bridges’ B1-B3, as used in ribosome nomenclature.
One thing I find useful to learn from this new structure map is how highly paired P5 and P7 are with P5 featuring GU pairs and P7 featuring AU pairs. This almost looks engineered!
Moving on, the other two structures are multimeric, meaning several copies of identical RNA come together to form a structure, in this case a hollow sphere. The ROOL sphere consists of 8 copies and the GOLLD sphere consists of 14 copies. These appear to be an entirely new class of structures.
Symmetric multimers are common among proteins and rationally designed RNA molecules, but observations of natural RNA multimers are rare. When observed, natural RNA homomeric interactions typically involve a single contact.
Both of these structure have numerous intermolecular contacts, referred to as bridges in the paper, that connect the individual chains (copies). The intramolecular contacts are drawn as lines as normal, and the intermolecular contacts are listed as B1, B2, B3, etc. (All of this makes them look even more like a Death Star to me.) Both structures form a nanocage larger than the ribosome!
The Rumen-Originating, Ornate, Large (ROOL) RNA consists of two half-shells, each formed by four chains (copies) of the 659-base RNA.
The mix of pairs in the long stems of the ROOL are more in line with what I typically see in natural RNA, although still a little heavy in AU pairs. I don’t have much more to say about the secondary structure except that AA non-canonical pairs are again more common than I would expect, and the lack of GU/UG crossing pairs makes sense since each RNA is essentially flat. (GU crossing pairs introduce flexibility.)
@DigitalEmbrace, again a supercool explanation of the article!
I was wondering about if there were a protein equivalent of this RNA Death Star. Like a selfassembling hollow ball.
It hit me where I had seen it before. The protein capsid (shell) of a virus. Those viral coat proteins are typically assembled of repeat monomers of the same protein. An advantage as the virus then only needs one gene for a coat protein. It just makes more of it.
The natural question now is, if a virus exist with an RNA coat shell
Also I wonder if RNA capsids will generally be smaller than protein capsids.
Ok, I think I can answer the latter one myself. The nanocages of those RNA balls can be larger than ribosomes. Ribosomes are similar in size to or much smaller than viral capsids.
The chaperonin GroEL GroES protein complex forms chambers to correct or assist protein folding. It’s ATP driven and has a pair of reciprocating chambers. While one GroEL chamber is occupied and closed off by a GroES cap, the other chamber can’t be used.
Vaults are another example of compartments formed by protein. Not much seems to be known about them. Also composed of two halves. About 95% protein and 5% RNA.
