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A class of RNA molecules protects germ cells from damage, Penn vet researchers show
Date:11/15/2012

ge during meiosis, called pachytene piRNAs, were also required for "silencing" transposons.

Working in male mice, the researchers manipulated an enzyme called MOV10L1, which is known to interact with piwi proteins and is believed to help produce piRNA molecules. They created a mutant mouse in which they could selectively inactivate MOV10L1 at specific stages before, during and after meiosis. The mice that lost the function of MOV10L1 before or at the pachytene stage of meiosis were sterile. When Zheng and Wang examined their germ cells more closely, they found that spermatogenesis had apparently come to a halt at the post-meiotic stage: Early stages of the germ cells were present, but the mice completely lacked mature sperm.

Further experiments allowed Zheng and Wang to pinpoint that MOV10L1 was playing a critical role at the pachytene stage. MOV10L1 mutants lacked pachytene piRNAs, but their levels of pre-pachytene piRNAs were unaffected, as the mutation was "turned on" after they had already been produced.

The researchers also found that, in the MOV10L1 mutants, piwi proteins congregated together along with mitochondria, suggesting that mitochondria may be involved in the generation or organization of pachytene piRNAs. Furthermore, the spermatids, or early-stage sperm, of the mutants had severe DNA damage. While the researchers suspected that the damage may have been caused because of transposons that had been freed from repression in the absence of piRNAs, they actually found that two common transposable elements were not de-repressed in the mutants. They also found a build-up of pachytene piRNA precursors in the testes of the mutants. Their findings raise the possibility that there is another mechanism by which damage occurs.

"It could be the accumulation of precursor molecules is causing some of the damage," Wang said.

This new function for MOV10L1, in playing an essential role in producing pachytene piRNAs, gives r
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Contact: Katherine Unger Baillie
kbaillie@upenn.edu
215-898-9194
University of Pennsylvania
Source:Eurekalert

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