produce RNA molecules with special properties and biological effects.
A common feature of such functional RNAs is that they tend to adopt a stable structure that enables them to interact with proteins and other molecules. These RNA structures involve the same kind of base pairing that holds together a double-stranded helix of DNA. UCSC researchers were able to demonstrate a stable structure for HAR1 RNA from humans and other vertebrates. Furthermore, 10 of the 18 changes in the human HAR1 sequence involved compensatory changes that preserved the base pairing in this structure.
"The HAR1 RNAs from both humans and chimps form stable structures, but there are significant differences," Salama said. "Our hypothesis is that these changes preserve the overall function of the molecule, but somehow alter its interactions with its binding partners. Those differences may have something to do with what makes our brain different from a chimp's."
Ongoing investigations may lead to more definitive findings about the function of HAR1, she said. Haussler noted that this project was one of the first to make use of the wet lab he established to explore and verify predictions generated from his group's computational genomic research.
"It's been very rewarding to see it all come together like this," Haussler said.
In addition to Pollard, Salama, Haussler, and Vanderhaeghen, the coauthors of the Nature paper include Nelle Lambert, Marie-Alexandra Lambot, and Sandra Coppens of the Institute for Interdisciplinary Research (IRIBHM) at the University of Brussels; Jakob Pedersen, Sol Katzman, Bryan King, Courtney Onodera, Adam Siepel (now at Cornell University), and Andrew Kern of UCSC's CBSE; Colette Dehay of the University Claude Bernard Lyon, France; and Haller Igel and Manuel Ares of UCSC's Center for Molecular Biology of RNA and Department of Molecular, Cell, and Developmental Biology.
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