Brain Development Is Guided by Junk DNA That Isn't Really Junk

Specific DNA once dismissed as junk plays an important role in brain development and might be involved in several devastating neurological diseases, UC San Francisco scientists have found.

In their own research, the UCSF team studies molecules called long noncoding RNA (lncRNA, often pronounced as "link" RNA), which are made from DNA templates in the same way as RNA from genes.

"The function of these mysterious RNA molecules in the brain is only beginning to be discovered," said Daniel Lim, assistant professor of neurological surgery, a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, and the senior author of the study.

Evidence indicates that lncRNAs can tether structural proteins to the DNA-containing chromosomes, and in so doing indirectly affect gene activation and cellular physiology without altering the genetic code. In other words, within the cell, lncRNA molecules act "epigenetically" -- beyond genes -- not through changes in DNA.

Alexander Ramos, first author of the study, conducted extensive computational analysis to establish guilt by association, linking lncRNAs within cells to the activation of genes. Ramos looked specifically at patterns associated with particular developmental pathways or with the progression of certain diseases. He found an association between a set of 88 long noncoding RNAs and Huntington's disease, a deadly neurodegenerative disorder. He also found weaker associations between specific groups of long noncoding RNAs and Alzheimer's disease, convulsive seizures, major depressive disorder and various cancers.