|Phillip Zamore, PhD|
UMass Medical School scientists working in the lab of Phillip Zamore, PhD, are the first to assemble the genome of the cabbage looper moth, a common vegetable pest. The cabbage looper genome is an important new model system for studying insecticide resistance and small RNAs, particularly the piRNAs that are critical to epigenetic inheritance. The cabbage looper is a distant cousin of Drosophila, the fruit fly that is one of the most common insect models for studying genetics. Piwi-interacting RNAs, also known as piRNA, are thought to be the largest class of small non-coding RNA molecules expressed in animal cells. The research was published in eLife.
“There are many evolutionary differences between flies and moths,” said Dr. Zamore, Howard Hughes Medical Institute Investigator, the Gretchen Stone Cook Chair of Biomedical Sciences and chair and professor of RNA therapeutics. “Yet they are still close enough that we can use this new model system to investigate rapidly evolving components of the genome.”
Zamore and colleagues used a combination of cutting edge genomic tools to find 14,037 protein coding genes, including chemoreception and detoxification gene families that may explain the pest’s ability to rapidly adapt to insecticides and other toxins. They also identified 295 microRNAs and 393 piRNA-producing sites, as well as 39 genes responsible for encoding small RNA pathway proteins. The researchers found that nearly the entire “W” chromosome of the cabbage looper is dedicated to the production of piRNA, the first time scientists have ever found a single chromosome responsible for coding piwi-interacting RNA.
An expert in RNA biology, Zamore said current efforts to study piRNA are hampered by a lack of model cell and animal systems.
“We know 90 percent of the piRNA pathway in humans and mammals,” said Zamore. “But we don’t understand the top of the pathway, the part that starts everything and tells the piRNA machinery ‘This is a bad genetic parasite, go and silence it,’ which remains unexplored outside of flies.”
One function of piRNA is to silence transposons, which are DNA parasites that can change their position within a genome, sometimes creating or reversing mutations and altering the cell’s genetic identity, promoting inappropriate exchange of DNA between chromosomes and causing deleterious effects.
“This process is unique to each animal, in part because these components are evolutionarily recent and more rapidly evolving, so there is much more variation between species,” said Zamore. “What we want to ask is how the cabbage looper silences these transposons and how that stacks up against the machinery we know of in Drosophila.”
By comparing the piRNA machinery of the cabbage looper to Drosophila, Zamore hopes to identify the different ways that animals might solve these problems. This in turn will lead to insights about how piRNA operate in mammals and humans.
The next step for Zamore and colleagues will be to develop a novel model organism system using the cabbage looper. “Ultimately, we want to be able to study piRNA in a cultured cell and take what we learn there back into the animal to confirm what we’ve found,” he said.
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