I saw a codon table in Brock’s Biology of microorganisms (page 204) recently and it made me think, that this would give a string of RNA a very different base distribution to what I knew from Eterna. It was a codon table over a bacterial species. I also looked up a codon table for humans, where the frequency of use is also mentioned.
When an alphabet of 20 amino acids is made of blocks of 3 bases (= codon) with just 4 letters, then there must be high number of more than one of the same base in line in messenger RNA. Just from pure statistics.
Of the 64 possible codon’s around, almost half (28 in the above table) have dinucleotides and trinucleotides in them. (Bases of the same kind in line). And they are generally among those with the higher frequencies. When codon’s gets put together, then even more bases of the same kind get the chance of being in line. Between just two codons put together this number of the same bases possible in line, ranges from 2 to 6. And amino acids can be even more of the same amino acid in line, though I don’t have a feel for how typical this is in proteins, compared to our RNA. I have just seen repeat amino acids sometimes in books.
I think what I mention above will make messenger RNA quite different to the RNA we are playing with, with the intent of getting it to fold into a very specific structure. Most of the RNA shapes we are playing with, loves variation and don’t like too many double bases or same turning base pairs for that matter, or more. Except for in longer stems that are more tolerant.
That made me think that our RNA must behaves different, as it is supposed to fold up in a very specific shape. Early I noticed that the bases liked to be twisted in relation to each other and generally varied, for the lab designs to do well. Though longer stems are a bit more tolerant of repeat bases.
From what I understand, messenger RNA also has a 3D structure. So it folds up as well. But I’m imaging a much more loose and less strong fold. I suspect that the tangle is not as tight as what can happen in our (mostly also shorter) and specific structured RNA, or like in tRNA.
If it is too strongly folded, will it then be able to unfold when it has to be read and made into protein? Which makes me think about how RNA like ours will get made in a cell. I’m thinking that all the double and more of the same base in line makes sure that the mRNA don’t get too tangled up in itself. That should make it easier for splicing and so on to happen.
I have read that base sequence can stop transcription. Actually there is a small sequence bit of the last part of the mRNA that folds into a hairpin and thus stalls and interrupts translation. I don’t know if the ribosome that makes mRNA into protein is equally prone to being stopped. It is a lot bigger than polymerase, so perhaps much more stable. As I understand it only gets stopped by stop codon’s. So that makes me think it might be stronger.
So here is what I think. Messenger RNA will have another base frequency of dinucleotides and more bases in line. By having these many of the same bases in line over a long stretch, it ensures that it doesn’t get folded too strictly, but is just loose enough to get untangled. I don’t know if it really is so. No matter what I find it fascinating that our RNA sequences appears to be so different from mRNA. And I’m mainly just trying to understand what it means.
It is my experience that double nucleotides or more is much more welcome in loop area, compared to stem. And loop exactly is characterized with being not binding (at least not most of the loop if it is bigger and the bases are well picked. So I’m imagining mRNA not being nearly as folded and tangled up as our kind of RNA, that is folding in a particular structure.
Which reminds me that about another thing I suspect, namely in case of a lot of base pair in line and turning the same way, I think they will be much easier to split, than stems with more flipped and varied content. Something I have earlier mentioned that I think double bases and more repeat bases, helps cause a stem to split and make it bind less strong.
Just to get a feel for what a mRNA could look like, I took a random mRNA from NCBI. Quite right there is a lot of same kind of bases in line. (this is the DNA template for the mRNA, so it shows DNA bases and not RNA bases.)
I also for the fun of it looked at some of the Eterna Classic designs. Vienna do generally have more repeat bases than Nupack and us players. Nupack usually scores better than Vienna and players start getting better scores as the shapes gets harder.
Im imagining something like this. Defined structure in our small structural RNA’s. And messy, but not too tangled structure for mRNA.
Question: Are messenger RNA more short lived than structurally folded RNA? I’m trying to understand what amount of repeat bases means for degradation speed.
Ok, let me hear what you guys think about this.