As scientists have added to a growing list of types of RNA molecules with roles that go beyond conveying the genetic code, they have found the short strands known as Piwi-interacting RNAs (piRNAs) particularly perplexing. New work from Howard Hughes Medical Institute (HHMI) scientists suggests those abundant molecules may be part of the cell's search engine, capable of querying the entire history of a cell's genetic past.
Organisms contain thousands of piRNA molecules, strands of 26 to 31 nucleotides encoded all over the genome. In two studies published online June 25, 2012, in the journal Cell, HHMI investigator Craig Mello of the University of Massachusetts Medical School has discovered that piRNAs may be responsible for detecting foreign RNAsuch as that carried by viruses -- relying on a complex search mechanism to reveal whether an invader is foreign based on prior gene activity.
"piRNAs are found in all animals and some of their functions in some organisms have been explained," says Mello. "But overall they've been a very mysterious category of molecule."
Some piRNAs have sequences that match up identically to genes elsewhere in the genome, suggesting that they bind and regulate those genes. But most have no perfect genetic match. Mello and his team focused their attention on the more puzzling piRNAs -- those that had no obvious targets.
In the worm Caenorhabditis elegans, the scientists unexpectedly found that foreign genes that they inserted into the genome were sometimes silenced and sometimes not. When they genetically modified the worm to lack the Piwi protein, the silencing no longer worked.
When the researchers probed which sequences piRNAs tended to shut down, they found that if a cell has ever turned on a gene in the past, the piRNA system will recognize it as a "self" gene and allow it to be expressed. But if it hasn't been active in the organism before, the piRNA will set the silencing mechanism into act
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| Contact: Jennifer Michalowski michalow@hhmi.org 301-215-8576 Howard Hughes Medical Institute Source:Eurekalert |
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