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| Human neural progenitor cells (green) and differentiated astrocytes (orange)--Courtesy of the National Institute of Neurological Disorders and Stroke |
A protein previously known for other functions has also been found to act as a switch that decides whether an immature neural cell stays in a stem cell-like state or differentiates into a functional neuron.
Detailed in Cell Reports, researchers from the University of California, San Diego, have found that this choice is controlled by UPF1, a protein essential for the nonsense-mediated RNA decay (NMD) pathway.
Up until now, NMD was believed to play two roles: to help cells get rid of faulty messenger RNA and to break down a specific group of normal mRNAs. Now, the UCSD team has found that, when working together with a special class of RNAs called microRNA, UPF1 triggers the deterioration of a particular mRNA that encodes a protein in the TGF-Β signaling pathway that promotes neural differentiation. By breaking down that mRNA, the cell fails to produce the encoded protein, which stops neural differentiation from occurring.
Since NMD is vital to normal brain development, the findings could have implications for the development of new therapies for neurological disorders, including autism and schizophrenia.
"Humans with deficiencies in NMD have intellectual disability and often also have schizophrenia and autism. Therapies to enhance NMD in affected individuals could be useful in restoring the correct balance of stem cells and differentiated neurons and thereby help restore normal brain function," said principal investigator Miles Wilkinson, a professor in the department of reproductive medicine and a member of the UC San Diego Institute for Genomic Medicine.
- see the press release
- read the study (PDF)