Ribozymes are thought to have played a pivotal role in the early evolution of life, but relatively few have been identified in modern organisms. We performed an in vitro selection aimed at isolating self-cleaving RNAs from the human genome. The selection yielded several ribozymes, one of which is a conserved mammalian sequence that resides in an intron of the CPEB3 gene, which belongs to a family of genes regulating messenger RNA polyadenylation. The CPEB3 ribozyme is structurally and biochemically related to the human hepatitis delta virus (HDV) ribozymes. The occurrence of this ribozyme exclusively in mammals suggests that it may have evolved as recently as 200 million years ago. We postulate that HDV arose from the human transcriptome.
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