to possible new drug targets
A new function has been identified for Jpx RNA, previously known for its
role in X chromosome inactivation, a key step in development of healthy female embryos

Date:
December 1, 2021
Source:
Massachusetts General Hospital
Summary:
Researchers have identified the first non-coding RNA that
controls formation of chromosome loops, which govern gene
expression. Jpx RNA was previously thought to be involved only
in X chromosome inactivation, a necessary step in development
of female embryos. This discovery could create new targets for
drug developers.



FULL STORY ==========================================================================
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
the journal Cell, could help create new targets for drug development.


========================================================================== Chromosomes are long, string-like structures made up of DNA, RNA and
proteins.

A chromosome must fold into a loop in order to fit into the nucleus of
a cell.

These loops bring together distant genetic material. "Genes and control elements -- sequences that regulate genes -- have to communicate with
one another for the cell to work properly," says the senior author of
the paper, Jeannie Lee, MD, PhD, of the Department of Molecular Biology
at MGH.

"Chromosome looping is kind of like bringing people together in a
conference room so they can talk to one another." These interactions
within a chromosome loop regulate gene expression, that is, whether
a gene is turned "on" and thus producing proteins or turned "off."
Chromosome loops are in constant flux, growing and contracting as they
change their composition of genes in response to environmental stimuli
and the body's developmental needs. Returning to the conference room
metaphor, a protein called CTCF acts as a door, explains Lee, and it
was already known that a chromosome loop may have multiple sets of
double doors -- some open, some closed. "But what wasn't known is how
these doors open and close," explains Lee. "Who are the gatekeepers?"
The answer proved to be a surprise. Lee and her team discovered that
a form of RNA known as Jpx is a gatekeeper that regulates the behavior
of CTCF in chromosome looping. Jpx RNA was no stranger to Lee and her
fellow investigators. 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.

However, Lee's group, which included postdoctoral fellow Hyun Jung Oh,
PhD, first author of the study, found that Jpx RNA also determines what combination of double doors are open at any given time by "evicting"
CTCF from the chromatin (a substance within a chromosome). "Jpx regulates whether multiple doors are open or just one, as well as which panels of
double doors are open, left or right," says Lee. "By regulating that
process, Jpx determines how big the chromatin loop is and, therefore,
which genes around the loop are expressed." Jpx is the first form of
RNA to be identified as playing a vital role in regulating the behavior
of CTCF, but there will be many others, predicts Lee.

That's exciting, she says, because there are probably 10 times more
varieties of RNA than there are proteins. While Jpx regulates genes
involved in 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 RNA could speed the development of effective
new medications.

========================================================================== Story Source: Materials provided by Massachusetts_General_Hospital. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Hyun Jung Oh, Rodrigo Aguilar, Barry Kesner, Hun-Goo Lee, Andrea
J. Kriz,
Hsueh-Ping Chu, Jeannie T. Lee. Jpx RNA regulates CTCF anchor
site selection and formation of chromosome loops. Cell, 2021; DOI:
10.1016/ j.cell.2021.11.012 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211201124313.htm

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