New Gatekeeping Function for Jpx RNA Identified

An important player in the healthy development of female embryos turns out also to play a key role in regulating the behavior of chromosome loops and gene expression in both sexes, according to a new study by researchers at Massachusetts General Hospital (MGH). These findings, reported in Cell, could help create new targets for drug development.

The team discovered that a form of RNA known as Jpx is a gatekeeper that regulates the behavior of CTCF in chromosome looping. Eight years ago, they showed that this noncoding form of RNA is a key player in the phenomenon known as X chromosome inactivation, which is essential for normal development in all female mammals, including humans. Jpx RNA helps count X chromosomes in female cells very early in development; if two are detected, one X chromosome is inactivated or silenced.

Now, the scientists found that Jpx RNA also determines what combination of double doors are open at any given time by evicting CTCF from the chromatin. “Jpx regulates whether multiple doors are open or just one, as well as which panels of double doors are open, left or right,” says lead researcher Jeanine Lee. “By regulating that process, Jpx determines how big the chromatin loop is and, therefore, which genes around the loop are expressed.”

While Jpx regulates genes involved early in the development of an embryo, other RNAs awaiting discovery may regulate the formation of chromosome loops that influence the risk for cancer, autoimmune disorders, and other diseases, says Lee. Identifying these RNAs could speed the development of effective new medications.