4.4 Article

A Hairpin Ribozyme Derived Spliceozyme

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CHEMBIOCHEM
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WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.202300204

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cleavage; hairpin ribozyme; ligation; spliceozyme; splicing

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The majority of RNA splicing in organisms today involves the regulated removal of introns from pre-mRNAs. A model of earlier life forms suggests that RNA splicing could have occurred by a hairpin ribozyme derived spliceozyme that cuts out introns and joins exons. The excised intron then acts as a positive regulator for a DNAzyme. This study demonstrates how small RNAs can perform complex RNA processing and deliver functional RNA molecules.
The vast majority of RNA splicing in today's organisms is achieved by the highly regulated and precise removal of introns from pre-mRNAs via the spliceosome. Here we present a model of how RNA splicing may have occurred in earlier life forms. We have designed a hairpin ribozyme derived spliceozyme that mediates two RNA cleavages and one ligation event at specific positions and thus cuts a segment (intron) out of a parent RNA and ligates the remaining fragments (exons). The cut-out intron then performs a downstream function, acting as a positive regulator of the activity of a bipartite DNAzyme. This simple scenario shows how small RNAs can perform complex RNA processing dynamics, involving the generation of new phenotypes by restructuring segments of given RNA species, as well as delivering small RNAs that may play a functional role in downstream processes.

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