One interesting facet of RNA biology is the matter of the occurrence and function of structural RNA units within RNAs inside of living cells. Excellent examples of these are the many so-called riboswitches, motifs that bind metabolites and alter the functionalities of RNAs in which they reside. As more and more examples of RNAs with catalytic activities become known, questions naturally arise as to whether such activities might impact RNA function in vivo. A recent study poses just such a question for what is among the simplest of known catalytic RNAs, namely the manganese-dependent ribozyme. This enzyme consists of little more that a GAAA-UUU complex. These two motifs, that need not be adjacent in the RNA, are expected to occur at a high frequency in natural RNAs. A recent report indeed finds that RNAs that possess such motifs indeed may be Mn-dependent ribozymes. The physiological signifiance of this finding is, in my opinion, a bit of an open issue. But the possibilities are fascinating. The last sentence of the abstract (that follows) is especially provocative.
The smallest catalytic RNA identified to date is a manganese-dependent ribozyme that requires only a complex between GAAA and UUU to effect site-specific cleavage. We show here that this ribozyme occurs naturally in the 3′-UTR of Vg1 and β-actin mRNAs. In accord with earlier studies with model RNAs, cleavage occurs only in the presence of manganese or cadmium ions and proceeds optimally near 30°C and physiological pH. The time course of cleavage in Vg1 mRNA best fits a two-step process in which both steps are first-order. In Vg1 mRNA, the ribozyme is positioned adjacent to a polyadenylation signal, but has no influence on translation of the mRNA in Xenopus oocytes. Putative GAAA ribozyme structures are also near polyadenylation sites in yeast and rat actin mRNAs. Analysis of sequences in the PolyA Cleavage Site and 3′-UTR Database (PACdb) revealed no particular bias in the frequency or distribution of the GAAA motif that would suggest that this ribozyme is currently or was recently used for cleavage to generate processed transcripts. Nonetheless, we speculate that the complementary strands that comprise the ribozyme may account for the origin of sequence elements that direct present-day 3′-end processing of eukaryotic mRNAs.
How deeply-rooted in the history of life is the polyadenylation signal? I think the idea suggested by Kolev et al. needs to be thought out in an evolutionary context that includes the likelihood that polyadenylation as envisaged by these authors may be a derived characteristic (see this essay for some thoughts along these lines). Keeping this in mind, I am not sure it makes sense. Nonetheless, the suggestion is intriguing and merits some debate.
The citation:
Kolev NG, Hartland EI, Huber PW. 2008. A manganese-dependent ribozyme in the 3′-untranslated region of Xenopus Vg1 mRNA. Nucl. Acids Res. 36, 5530-5539.
The RNA Underworld 