mRNA Self-cleavage: Another Strategy for Gene Expression Regulation

Source: Martick et al. (2008). A discontinuous hammerhead ribozyme embedded in a mammalian messenger RNA. Nature 454:899-902.

Hammerhead ribozyme is an RNA with catalytic activity which is capable of self-cleavage. The authors, attest the hypothesis that ribozymed may reside in mRNA and thus control the stability of the mRNA through auto-catalytic self-cleavage. They found three occurrences of hammerhead ribozyme in rodent 3' UTRs; Clec2d and Clec2e (which are paralogs) and Clec2d11 (a homolog of Clec2d). Subsequent homology searches succeeded in finding homologs of these genes in other mammals as well (e.g. horse and platypus). Below you see the general secondary structure of these embeded ribozymes.


Using the Clec2d and Clec2e in vitro transcription, the authors showed that cleavage takes place at the predicted sites; whereas, in transcripts with a mutant ribozyme the transcript stays intact. They also used reporter constructs to test the expression level of lucipherase gene in the presence and absence of this ribozyme in its 3' UTR. They showed that addition of this ribozyme downregulates the transcript level.

Overall, this is a very intersting paper introducing a new strategy for gene regulation. I guess there are many more of these mechanisms are waiting to be found. However, these strategies, as elegant as they are, are far from universal.