Penn Biologists Develop New Method for Studying RNA

January 7, 2014

Scientists at the University of Pennsylvania and colleagues have teamed up to offer a new method for elucidating RNA regulation. Since RNA is now believed to play a major role in determining whether and how DNA is turned into a protein product, the scientists have provided a means of efficiently obtaining an entire “footprint” of interactions between RNA and the proteins that bind to RNA molecules.

The senior author on the paper, published in a special issue of the journal Genome Biology, is Brian Gregory, Assistant Professor in the Department of Biology. The research was co-led by doctoral students Ian M. Silverman and Fan Li, and graduate student Anissa Alexander also contributed. The Penn team collaborated with Loyal Goff, Cole Trapnell, and John L. Rinn of Harvard University.

The researchers focused their study on RNA binding proteins, or RBPs. Every step of an RNA molecule’s life cycle is controlled by this type of protein, so they created a database—akin to DNA footprinting—of everywhere an RNA is being touched during its life cycle. These sites of interaction could be significant when it comes to diseases that are associated with RNA.

Having the full footprint of RNA-RBP interactions is important to reveal cases where a combination of interactions is necessary to achieve a certain regulatory result, and could turn up other patterns of interest, such as particular RNA sequences that appear more often than expected. Mutations in regions of RNAs where RNA proteins are bound have huge effects, particularly in the brain.

Through their database, the team found that when mutations associated with early-onset Parkinson’s disease were introduced into RNA probes, specific RBP-RNA interactions were affected. This observation supports the growing characterization of certain genetic illnesses, especially neurological ones, as “RNA diseases.”

The researchers also noted that their method will allow other scientists, including those who have up until now focused on DNA mutations’ role in disease, to examine their data for the possible involvement of RNA defects. To encourage this type of investigation, the team has made this data publically available on the Web.

The study was supported by the National Science Foundation, the National Human Genome Research Institute and the National Institute for General Medical Sciences.

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