Role of Small RNAs in DNA Validation

Researchers using the protozoan Tetrahymena as a model have elaborated a complex DNA error correction system that is of ancient origin and may still be active in most organisms, including man. The mechanism ensures that any foreign genetic material that has been inserted into the cell's DNA is neutralized before being passed on to the next generation. Their work was reported in the September 20, 2002, issue of Cell.

Tetrahymena differs from mammalian cells by having more than one nucleus. It maintains different versions of its DNA in each of its two nuclei. The smaller nucleus (the micronucleus) is a storage receptacle for one copy of the cell's genome. The larger nucleus (the macronucleus), on the other hand, uses a second copy of the DNA to regulate the cell's life functions. The macronucleus houses about 15% fewer DNA sequences than the smaller one, and when the cell mates to create a new generation of cells, this large macronucleus withers and dies. New micro- and macronucleus are generated based on the template in the micronucleus.

During the chromosome rearrangements involved in the regeneration of the two nuclei, specific regions of DNA are eliminated and flanking regions are healed, either by religation or construction of telomeres. The original macronucleus then withers away, leaving the new macronucleus and the micronucleus, both of which divide as the cell divides into identical daughter cells, each with a new set of nuclei.

The investigators, from the University of Rochester (NY, USA), identified a gene, TWI1, which is homologous to piwi and is required for DNA elimination. They also found that small RNAs were specifically expressed prior to chromosome rearrangement during conjugation. These RNAs were not observed in TWI1 knockout cells and required PDD1, another gene required for rearrangement, for expression.



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