Structured outlook

RNA drug developers get a boost from mass discovery of functional mRNA structure

A Cell study capturing hundreds of E. coli mRNA structures makes the case that complex, functionally relevant RNA structures are the rule, not the exception, and builds confidence that mRNAs -- once widely considered undruggable -- could furnish a broad reservoir of new targets. The question is whether the study’s findings will extend to mammalian cells.

For years, the prevailing assumption was that the only key information in mRNA lies in its primary structure -- the linear sequence that dictates the proteins it encodes; the three-dimensional structures of mRNAs were not thought to be important for their functional roles.

The new findings, from a group led by Ribometrix Inc. founder Kevin Weeks, showed that most mRNAs in E. coli are in fact highly structured, and those structures control the rates at which mRNAs are translated. The group found that almost all of the 400 mRNA structures profiled controlled the efficiency of translating mRNA into proteins by modulating ribosome binding, among other processes.

Weeks is a professor of chemistry at University of North Carolina at Chapel Hill. His spinout Ribometrix is one of a spate of companies formed in the last few years to develop small molecule therapeutics that bind RNA.

According to Weeks, there has been increasing recognition that mRNA can form complex structures, but detailed observations have been limited to specific transcripts. This study’s scale allowed far more extensive conclusions to be drawn.


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