Fragile X syndrome, the most common form of inherited intellectual disability, may be unfolding in brain cells even before birth, despite typically going undiagnosed until age 3 or later. A new study showed that FMRP, a protein deficient in individuals with fragile X syndrome, has a role in the function of mitochondria, part of a cell that produces energy, during prenatal development.
Fragile X syndrome, the most common form of inherited intellectual disability, may be unfolding in brain cells even before birth, despite typically going undiagnosed until age 3 or later.by researchers at the University of Wisconsin-Madison showed that FMRP, a protein deficient in individuals with fragile X syndrome, has a role in the function of mitochondria, part of a cell that produces energy, during prenatal development.
In previous research, Zhao found that mitochondria in mice with an FMRP deficiency that imitates FXS were smaller and unhealthy. Diving deeper, they also discovered that FMRP regulates genes involved in mitochondria fission-fusion, a process into which mitochondria fuse into a bigger shape in order to produce more energy for the cell.
Although it has been long known that FMRP is deeply involved in FXS, the new discovery pinpoints a role for the protein in early development of the condition. FMRP is protein that regulates the use of messenger RNA, sort of a of working copy of DNA used to produce the proteins that make things happen in cells. The researchers found that many of the mRNA strands that interact with FMRP are implicated in autism, providing a molecular link between FXS and autism spectrum disorder. Unexpectedly, many FMRP-bound mRNAs are expressed by genes classified as essential -- genes that are very busy during prenatal development but less active after birth.
Next, Zhao wants to do a detailed biochemical analysis of mitochondrial dysfunction and figure out which key proteins are less present in FXS-affected neurons. She is also working on better understanding how RACK1 and leflunomide work to rescue mitochondrial function.
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