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Study Of Life’s Tiniest Architects Could Lead To New Opportunity To Treat Cancers

If a is the blueprint for life, then the chief architects are tiny slices of genetic material that orchestrate how we are assembled and function, Yale School of Medicine researchers report in the journal Developmental Cell.

The study pinpoints the molecular regulators of epigenetics – the process by which unchanging along our DNA are switched on and off at precisely the right time and place.

“Our genome is like a landscape with lakes, mountains, and rivers, but it is not yet a community or a city full of buildings,” said , director of the Yale Stem Cell Center and senior author of the study. “What this system does is decide where and when to send out the masons, carpenters, and electricians to build a city or a community.”

In the past 20 years, scientists have discovered that some proteins, called , traverse the static genome and turn the genes on or off. The staggering number of potential combinations of active and inactive genes explains why a relatively small number of genes can carry out such a wide range of functions. But what guides these to their target? The answer, the has found, is specialized RNAs called piRNAs.

In the latest study, the Yale team discovered that piRNAs guide epigenetic factors to numerous sites throughout the genome of the fruit fly Drosophila, where these switches work to turn genes on or off. The dramatic change in gene expression patterns found illustrated piRNAs key role in coordinating biological activity.

“This is the first major mechanism discovered that controls where epigenetic factors – the gene switches – are to be placed in the genome,” Lin said.

Several types of cancers appeared to be triggered when the wrong kinds of piRNAs guide epigenetic factors to activate the wrong genes. Blocking the action of these piRNAs should become a new opportunity to treat cancers, Lin said.


Xiao A. Huang and Hang Yin of Yale are co-lead authors of the paper.
The research was funded by a National Institutes of Health Pioneer Award to Haifan Lin and a grant from to Lin and former Yale professor and co-author Michael Snyder, now of Stanford University.
Yale University