RNA-Binding Proteins Found To Play Regulatory Role in Synaptic Transmission

Scientists at the Ludwig-Maximilians-Universitaet in Munich have shown how RNA-binding proteins (RBG) modulate synaptic responses that mediate the transmission of nerve cell impulses. Their findings were published in Cell Reports. 

As a part of their study, the team characterized two of these RNA-binding proteins. Named Staufen and Pumilio respectively, the proteins are known to have essential functions in the central nervous system. Both are involved in the regulation of synaptic transmission, and they share a common set of target RNAs. They can even be found in the same RNA granules. "The functional interactions between the two RNA-binding proteins and the nature of the signaling pathways that they regulate in nerve cells had remained unknown up to now,” says Rico Schieweck, lead author of the new report.

Using cultured nerve cells, Kiebler's research group has now shown that Staufen and Pumilio control the activity of synapses in quite distinct ways. Staufen primarily controls mRNA levels and thereby the number of proteins they encode. Pumilio, on the other hand, regulates directly the process of mRNA translation and controls how much protein is synthesized per mRNA molecule. In fact, it plays a dual role in the synaptic transmission itself. 

"We demonstrated that Pumilio is a hitherto unrecognized coordinator of inhibitory synapses, and therefore regulates the excitability of neuronal synapses," Schieweck explains. If the gene for Pumilio is deleted, synapses become hyperactive, and the overall level of neuronal activity increases. Based on their results, Kiebler and his colleagues propose that Pumilio and Staufen can be regarded as yin and yang factors, which together control the expression of synaptic proteins. Thanks to their differential and highly selective effects on a variety of processes, they sensitively tune the activity of individual synapses.

Disruption of the neuronal equilibrium is a hallmark of neurological and neuropsychiatric disorders, such as epilepsy and autism. The researchers believe that their findings will contribute to a better understanding of these conditions because they provide insight into the mechanisms that enable different RNA-binding proteins to alter the functional characteristics of synapses.