It has been long known that RNA is a key player in genetic regulation. Recently, new research revealed that even the wiring of motor neurons and muscles (which controls body movement) is regulated at the RNA level. From the 1980s, it was thought that a protein called Z+ agrin is the major factor in the formation of the neuromuscular junction. Researchers from the Rockefeller University conducted experiments on mice to determine the splicing factor which is responsible for the extra piece of RNA (the Z+ exon) in Z+ agrin, which exists only in neurons. Not only did they discovered the splicing factor, they also found that this factor is the master regulator in the development of the neuromuscular junction.
The splicing factor was identified as NOVA, which exists in 2 different forms – NOVA1 and NOVA2. Genetically engineered mice that lacked both forms of NOVA (which in turns lead to no Z+ agrin) were found to be paralysed from birth, with the mice having few receptor clusters on their muscles. The researchers then inserted Z+ agrin into the mice, which to their expectation would cure the mice from paralysis. However, the mice still could not move, even though an examination of the morphology of the neuromuscular junction showed that the receptor clusters and synapses have been restored by the Z+ agrin.
The researchers then decided to examine the motor neuron and discovered that through artificial stimulation, it was able to transmit electrical impulses and cause the muscle to twitch, but the mouse remained paralysed. This led the researchers to conclude that although Z+ agrin restores the clusters of receptors at the neuromuscular junction, it is the work of “one or more of the many NOVA-regulated transcript” that provides the motor neurons with the ability to fire. This discovery is crucial by opening up a whole new perspective on the ability of RNA-binding protein to regulate neuronal function.
By Joshua Tay
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Article:
Rockefeller University (2009, March 17). RNA: Master Regulator Of Motor Neuron Firing Discovered. ScienceDaily. Retrieved March 22, 2009, from http://www.sciencedaily.com¬ /releases/2009/03/090315091400.htm
Additional Information:
Ruggiu et al. Rescuing Z agrin splicing in Nova null mice restores synapse formation and unmasks a physiologic defect in motor neuron firing. Proceedings of the National Academy of Sciences, 2009; 106 (9): 3513 DOI: 10.1073/pnas.0813112106
