Researchers will develop the RNA encyclopedia

The National Human Genome Research Institute has awarded genomics expert Brent Graveley and his team $5.6 million to continue working on a massive encyclopedia of human RNA molecules and proteins that bind to it. The grant is awarded jointly to Graveley and Gene Yeo of the University of California, San Diego.

RNA has a moment. Both the virus that causes COVID-19 and the rapidly developed vaccine against the virus are made of it, and the apparent success of this RNA engineering has invigorated research in this area.

RNA is essentially a string of chemical letters, closely related to DNA, which is translated into proteins and can be transported around our cells. The human body makes a lot of RNA for its own needs, and we don’t know what much of it does.

The Chair of the Department of Genetics and Genome Sciences and Professor Brent Graveley of the UConn School of Medicine and his lab have worked tirelessly to fill these gaps. Over the past 10 years, they have classified 563 of the proteins that bind RNA as part of the Encyclopedia of DNA Elements (ENCODE) project. The project funded by this new grant is called ENCORE (Encyclopedia of RNA Elements) and will allow them to classify even more, and make it a sort of reference work. Do you have RNA? It’s the proteins that bind to it, and that’s what they could do. Got a protein? These are the RNAs it binds and where they can be found.

Graveley’s and Yeo’s teams test each protein against different RNA extracts. If a specific protein binds only a few hundred RNA snippets and each of them contains the RNA sequence GACGAC, you can infer that the protein likes to bind to that sequence.

“Then you can look at a virus. If you see that same sequence in its viral RNA, you can guess which proteins might bind the RNA and where on the RNA those proteins might bind,” says Graveley. And if you know that, you might be able to design a treatment that stops it from binding and wreaking havoc in the body.

More generally, many researchers have a favorite gene to work on. Now these researchers can go to the ENCORE website and get a list of all the different proteins that could bind to their RNA of interest, and use them to formulate new hypotheses. Already, thousands of research projects have benefited from the database and the 563 proteins that Graveley and Yeo’s groups have already classified. To complete the database, the team only has about 1,500 to sift through.

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