One Gene to Regulate Them All (or, at least many of them)

I have recently written about the complexities of the underlying genetics of autism, including issues of gene regulation. That particular article focused on RNA regulation through methylation. Now there is more evidence for the importance of RNA regulation in Nature. The CPEB-4 protein is involved in the addition of the poly-A tail to mRNAs, and there is a version that specifically regulates this in genes connected to autism.

Each mRNA–which allows the genes for proteins to be turned into those proteins–has a tail of adenosines (one of the nucleotides) added to it after it is transcribed from the DNA. This is important because when the mRNA is translated into a protein, a nucleotide is removed from the end of the RNA. The longer the tail, the more proteins can be made. If only short tails can be produced, there will not be enough proteins produced. CPEB-4 seems to be involved in regulating the length of the poly-A tail.

As already mentioned, things in the cell are complex. In learning more about this gene, I have learned that the protein, cytoplasmic polyadenylation element binding protein, is found in the dendrites and cell body of neurons, but that “treatment of neurons with ionotropic glutamate receptor agonists causes CPEB4 to accumulate in the nucleus. ” Here we again see a gene/protein related to autism connected to glutamate. Stress conditions in the brain–low oxygen or glucose, for example–cause CPEB4 to be sent from the cytoplasm to the nucleus, where they cannot do their job of regulating poly-A in the cytoplasm.

As noted, the CPEB4 gene seems to be central, but that doesn’t mean we should necessarily see mutations in it connected to autism. There could be mutations in the gene(s) for the ionotropic glutamate receptor, or in the gene(s) for glutamate production, or in some other regulator of CPEB4. So while you are bound to find popular articles out there crowing about the fact that there is a “central gene” connected to autism, don’t be mistaken: it’s still a complex situation.


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