Researchers in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine have identified a new regulatory target for the Fragile X mental retardation protein (FMRP) -- laying the groundwork for possible new treatments for Fragile X syndrome (FXS), the leading inherited form of mental retardation.
The findings, published in the June Proceedings of the National Academy of Sciences, also have implications for autism, which shares a common physiological pathway with FXS.
Fragile X syndrome is mainly caused by a mutation in the FMR1 gene on the X chromosome that leads to the loss of FMRP, which is abundantly expressed in the brain and testes. Without this protein, brain development is hampered and nerve cells cannot communicate with each other appropriately, resulting in the reduced ability to learn and memorize. FXS affects about one in 4,000 males and one in 8,000 females. About 20% of children with FXS have autism and about 5% of autistic children have FXS.
The research team -- led by Dr. Yingqun Huang, assistant professor in Yale Ob/Gyn -- previously found that FMRP interacts with a nuclear mRNA export protein, NXF2, in the mouse brain and testes. In this study, the team used mouse neuronal cells to explore the functional characteristics of this interaction.
"We found that FMRP, together with NXF2, acts to down-regulate the expression of its target, the messenger RNA that encodes NXF1, which is an essential protein needed to transport most mRNAs from the nucleus to the cytoplasm of cells," says Huang. "Our findings explain why the NXF1 protein level is much lower in the hippocampal neurons involved in learning and memory than in many other cells. This may suggest that a high level of NXF1 might hinder the function of these cells."
"We are one of the first two labs to show that FMRP regulates gene expression at the mRNA stability level," Huang adds. "The idea is to find the mechanisms underlying the function of FMRP so in the future, we can develop more effective interventions."
According to Huang, future studies will look more closely at how FMRP works with NXF2 to regulate its targets. "We expect to identify more targets which are regulated by FMRP and NXF2. This will be a new direction in the FMRP research field," she says.
Other authors of the study included Meiqin Zhang of both Yale and Fudan University and Qiaoqiao Wang of Yale.
-- By Karen Peart
T H I S
W E E K ' SS T O R I E S
Yale to increase medical and scientific research programs
with acquisition of the Bayer HealthCare complex
Acquisition to expand Yale's economic impact
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COMMENCEMENT 2007
With pomp, Yale celebrates its newest graduates
Baccalaureate Address
Honorary Degrees
Outstanding teachers and students are awarded prizes
Former Yale gallery director has been elected an alumni fellow
NASA administrator is appointed University's first CFO
'Lights, cameras and action!' come to campus
Delegations travel to Brazil and Mexico for alumni-hosted events
Initiative seeks to promote effective use of solar power
Air pollution is shown to harm pregnant woman
SCHOOL OF MEDICINE NEWS
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Students' research on wood frogs is featured in Peabody exhibit
In Memoriam: Naturalist Charles L. Remington
Performances will showcase talents of young playwrights
New Yale website illustrates the history of slavery in Connecticut
Campus Notes
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