This is officially the first time I actually say something "serious" about science on this blog. I don't know if there are any who will read this who will have the knowledge to even understand this, but I mainly want to record this somewhere in the off case that it turns out to be correct.
Anyway, I have had a long-standing interest in the ribosome, and recently I read a structural paper in Cell reporting the structure of the ribosome in complex with a ribonuclease called RelE. This is a heck of a weird RNase, as it cuts messenger RNA as it is being translated, in the middle of a codon that's about to be read.
The authors show very convincingly that the RNA is NOT cleaved between the first and second nucleotides of the codon, but that it is cleaved between the second and third nucleotide. In the structure, this site lines up with a site on RelE that corresponds to the active site in a number of related RNases, and that's all well and good.
On the other hand, there's a small (or maybe big) problem here. All possible catalytic residues are more than 5 Angstroms from the scissile bond in both ribosomes, except maybe for Arg 81, which is mutated to Ala. In fact, there is not a single contact made to this phosphate. Furthermore, the 2' -OH nucleophile is positioned in a stereochemically awkward manner, that would require a large rotation of the phosphate to allow attack opposite the 5' -OH leaving group (See Figure 4B in the paper). In contrast, in the related nuclease (Fig. 4A), if you take the phosphate oxygen near the catalytic His 92 as the leaving group mimic, the 2' -OH of the guanine is a nice 180 degrees from it. While a rotation is certainly not impossible, and may be hindered here by the 2' O-methyl modification of the adenine, it seems it would require a significant movement of the guanine ribose.
What is most intriguing, though, is that in one ribosome the next phosphate, the one separating the current A-site codon from the next, appears better poised for attack. Not only would the required rotation of the phosphate be only about 60 degrees, rather than 120 degrees for the preceding phosphate, but this could be well accommodated without much movement of either ribose. In addition, if the 2' -OH were not methylated, it would probably move to hydrogen bond with the N3 of C 1054. Finally, the residue Arg 56 is both near the 2' -OH and the leaving group.
This immediately suggests that there may have been a primordial ribozyme-like activity in which C 1054 activated the 2' -OH of the third nucleotide for attack on its phosphate, and was assisted by some group playing the role of Arg 56, both helping activate the nucleophile and promote leaving group departure. In fact, when I had viewed the pre-cleavage state structure before reading the biochemical evidence for the scissile bond being in the other position, and not being familiar with other RNases, I just assumed that this was the scissile phosphate in the modern RelA.
In turn, this prompted the (maybe crazy) idea that possibly such an activity remains even today, and when the mRNA is cleaved after the third base, this makes the third base (i.e., the G) more mobile, allowing it to better align to be cut again at the site identified by the authors. While such a complicated cascade "violates" Occam's razor, its advantage would be that it provides a way to guard against excessive activity of a potentially toxic enzyme like RelA, particularly if the first cut were reversible.
Unfortunately, only the 5' fragment was isolated. If two successive cuts were made, this fragment would be the same, but the 3' fragment would be one nucleotide shorter, and a free 2'-3' cyclic GMP would be formed. This may be totally off, but on the other hand the thought was too striking not to write down somewhere.