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Wistar Scientists Find Surprising New Role for RNA in Gene Promotion

Despite progress in decoding the genome, scientists estimate that fully 95 percent of our DNA represents dark, unknown territory. Ramin Shiekhattar, Ph.D., Wistar’s Herbert Kean, M.D., Family Professor, sheds new light on the genetic unknown with the discovery of how long non-coding RNA (ncRNA) drives how cells “read” genes, transcribing the genetic code into proteins. He and his colleagues believe these long ncRNA molecules may represent so-called gene enhancer elements—short regions of DNA that can boost the amount of proteins a cell makes.  

These findings, published in the journal Cell, join a growing body of evidence that the classic “central dogma” of genetics is incomplete. In the central dogma, chromosomal DNA is transcribed into RNA, which is then translated by the cell into proteins. In recent years, however, scientists have found that not all transcribed RNA molecules become translated into proteins. In fact, 

studies have shown that whole swathes of the genome are transcribed for unknown reasons and to unknown effect. 

In the present study, Shiekhattar’s team pinpoints 3,000 long ncRNAs and estimates that there could be a total of between 10,000 to 12,000 long ncRNA sequences within our DNA.  Most long ncRNAs are encoded in DNA near genes known to be important to both stem cells and cancer. This suggests that targeting ncRNAs may represent a new strategy in slowing cancer growth.

“We are excited, first of all, because this is a new discovery about the very nature of human DNA; a new class of genetic object and a new layer of genetic regulation,” said Shiekhattar, a professor in Wistar’s Gene Expression and Regulation Program. “Secondly, we may have solved, in part, a great mystery in modern genetics.”