"It's a balancing act," said Guttman. "To maintain the pluripotent state, you need to repress differentiation genes."
The researchers also uncovered a critical clue about how lincRNAs carry out their important job. Through biochemical analysis, they found that lincRNAs physically interact with key proteins involved in influencing cell fate to coordinate their responses.
"The lincRNAs appear to play an organizing role, acting as a scaffold to assemble a diverse group of proteins into functional units," said John Rinn, an author on the paper, an assistant professor at Harvard University and Medical School, and a senior associate member of the Broad Institute. "lincRNAs are like team captains, bringing together the right players to get a job done."
"By understanding how these interactions form, we may be able to engineer these RNAs to do what we want them to do," said Guttman. "This could make it possible to target key genes that are improperly regulated in disease."
Aviv Regev, an author on the paper, a core member of the Broad Institute, and associate professor at MIT, sees the team's approach to studying the lincRNAs as important for the field. "Many people are interested in lincRNAs, but they need a comprehensive view of the whole collection of lincRNAs," said Regev. "The large-scale data and technology from this study will be useful for scientists worldwide in studying both lincRNAs as well as many other RNAs in the cell."
|Contact: Haley Bridger|
Broad Institute of MIT and Harvard