Small RNA-directed DNA elimination: the molecular mechanism and its potential for genome editing

Transposable elements have both detrimental and beneficial effects on their host genome. Tetrahymena is a unicellular eukaryote that deals with transposable elements in a unique way. It has a separate somatic and germline genome in two nuclei in a single cell. During sexual reproduction, a small RNA directed system compares the germline and somatic genome to identify transposable elements and related sequences. These are subsequently marked by heterochromatin and excised. In this Review, current knowledge of this system and the gaps therein are discussed. Additionally, the possibility to exploit the Tetrahymena machinery for genome editing and its advantages over the widely used CRISPR-Cas9 system will be explored. While the bacterial derived CRISPR-Cas9 has difficulty to access eukaryotic chromatin, Tetrahymena proteins are adept at acting in a chromatin context. Furthermore, Tetrahymena based gene therapy in humans might be a safer alternative to Cas9 because the latter can trigger an immune response.

Automated summary

Tetrahymena uniquely deals with transposable elements by having separate somatic and germline genomes in a single cell. During sexual reproduction, a small RNA directed system compares the two genomes to identify and process transposable elements. The chromatin context in Tetrahymena allows for potential advantages in genome editing and gene therapy compared to the CRISPR-Cas9 system.