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Young Investigator Profile: Yue Wan

Fellow, Genome Institute of Singapore

Recommended by Howard Chang, Stanford University

NEW YORK (GenomeWeb) – RNA can fold up into a variety of different shapes and take on different structures. Those shapes and structures can then influence how that RNA interacts with other RNA molecules and proteins.

But studying RNA structure is typically a time-consuming process. Traditionally, Yue Wan said, RNAs are probed and studied one at a time and sometimes, depending on their size, piece by piece. That, she said, was way too tedious.

Further, she added, studying bits of RNA rather than full-length versions might not give researchers an accurate picture of what the RNA structure is as it might fold differently when it's smaller.

As a graduate student, she worked on ramping that up so that thousands of RNA structures could be probed at once and at full-length.

"That will open a lot of doors because now we can not only study how one RNA folds to achieve its function, we can look at families of RNAs," Wan told GenomeWeb.

Now in her own lab at the Genome Institute of Singapore, Wan is tackling similar questions of RNA structure and function. She and her team are examining whether they can use structural approaches to uncover functional RNAs and whether these RNAs function differently under various conditions.

For instance, she said that RNA could fold differently based on what RNA binding proteins are bound to it. In one cell, RNA could fold one way, and in another cell with different RNA binding proteins present that RNA could take on a different conformation than it had in the first cell.

"We are really interested in understanding the dynamic regulation of RNA structure and how it contributes to RNA biology under different conditions," she said.

Wan noted that she's had to be selective about what projects she's started, as her lab is so new and currently has limited manpower. Recruiting people to her lab has been a challenge, she noted, both because she is still establishing her name and because many people have gone abroad for their training.

Paper of note

Wan was co-first author with the Weizmann Institute of Science's Michael Kertesz on a 2010 Nature paper that described an approach for profiling the secondary structure of thousands of mRNAs at a time.

This method, dubbed parallel analysis of RNA structure, or PARS, is based on the deep sequencing of RNA that had been treated with structure-specific enzymes like RNase V1 and S1 nuclease. Using this, they reported being able to determine the structural profiles for more than 3,000 transcripts from Saccharomyces cerevisiae.

"That paper I felt like really trained me as a scientist, whereby I actually had to develop the entire approach from scratch, and then Michael, [my] collaborator, did the computational stuff from scratch," she said. "That really taught me a lot about how to be a scientist."

Looking ahead

In the not-too-distant future, Wan said that more and more RNA structure studies would be done in vivo. By studying RNA structure in vitro, she noted that a lot of their usual environment — interactions with RNA-binding proteins or with other RNAs — is lost.

"I anticipate looking at more and more studies studying the dynamics of RNAs inside cells under different conditions," she said. For example, she said that future work could focus on how RNA structures change in the presence or absence of certain binding proteins or as cells differentiate.

Additionally, single-molecule approaches will be a boon to the field, according to Wan. Currently, most RNA studies look at a mixture of molecules, and being able to look at them individually will enable researchers to study why individuals RNAs take on certain conformations.

And the Nobel goes to…

"I would want to win it for identifying new functional classes of RNA that does something crazy that no one ever thought that RNA could do," Wan said.

This is the sixth in a series of Young Investigator Profiles for 2015 that will appear on GenomeWeb over the next few months.