Summary: A new study explores how neurons adapt their function to respond to stimuli quickly.
Source: University of Basel.
Neurons in the brain store RNA molecules – DNA gene copies – in order to rapidly react to stimuli. This storage dramatically accelerates the production of proteins. This is one of the reasons why neurons in the brain can adapt quickly during learning processes. The recent results of a research group at the University of Basel’s Biozentrum have been published in the current issue of “Neuron”.
Our brain is not only the most complex organ of the human body, it is also the most flexible. But how do neurons in the brain adapt their function in response to stimuli within a very short time frame?
The research group of Prof. Peter Scheiffele at the Biozentrum, University of Basel, has demonstrated that neurons store a reserve stock of RNA molecules, copies of the DNA, in the cell’s nucleus. These RNA molecules form the blueprint for new proteins. After a neuronal stimulus, the stored RNA molecules are mobilized in order to adjust the function of the neuron. The process of RNA synthesis (DNA copying) is very slow, especially for large genes. Thus, this newly uncovered mechanism for mobilization of stored RNAs saves time and provides new insights regarding the fast adaptation of the brain during learning processes.
Storage for RNA molecules
The RNA blueprint for proteins is produced by a sophisticated copying process: First, a basic RNA copy of the DNA is generated. From this copy, individual sections, so-called introns, are subsequently cut out to provide a finalized blueprint for the production of a specific protein. This process is called RNA splicing.
So far, it was assumed, that neuronal stimuli trigger the complete process for the production of new RNA molecules. However, the team of Peter Scheiffele now discovered that neurons in the brain pre-manufacture certain immature RNA copies which are only partially spliced. These RNA molecules still contain some introns and are stored in the cell nucleus. Signals induced by neuronal stimulation trigger the splicing completion of the immature RNA molecules.
“The copying process of the DNA, the so-called transcription, is already finalized in advance by the neurons. Hence, mature RNA molecules can be produced within minutes,” explains Oriane Mauger, the first author.
Prepared copies save time
For large genes, the production of the initial version of the RNAs itself takes dozens of hours. “The fact that the RNA molecules are already available in an immature form and only need to be completed, shortens the whole process to a few minutes”, says Mauger. “Since the transcription is very time-consuming, the storage of RNA means a significant time saving. This enables neurons to quickly adapt their function.”
“This study reveals a completely new regulatory mechanism for the brain”, declares Scheiffele. “The results provide us with a further explanation of how neurons steer rapid plasticity processes.”
Source: Heike Sacher – University of Basel
Image Source: NeuroscienceNews.com image is credited to University of Basel, Biozentrum.
Original Research: Abstract for “Targeted Intron Retention and Excision for Rapid Gene Regulation in Response to Neuronal Activity” by Oriane Mauger, Frédéric Lemoine, and Peter Scheiffele in Neuron. Published online December 21 2016 doi:10.1016/j.neuron.2016.11.032
Abstract
Targeted Intron Retention and Excision for Rapid Gene Regulation in Response to Neuronal Activity
Highlights
•PolyA+ transcripts can stably retain select introns and be confined in the nucleus
•Some of these intron-retaining RNAs rapidly undergo splicing upon neuronal activation
•Spliced transcripts are exported to the cytosol and loaded onto ribosomes
•The activity-dependent intron excision process requires NMDAR and CaMK pathways
Summary
Activity-dependent transcription has emerged as a major source of gene products that regulate neuronal excitability, connectivity, and synaptic properties. However, the elongation rate of RNA polymerases imposes a significant temporal constraint for transcript synthesis, in particular for long genes where new synthesis requires hours. Here we reveal a novel, transcription-independent mechanism that releases transcripts within minutes of neuronal stimulation. We found that, in the mouse neocortex, polyadenylated transcripts retain select introns and are stably accumulated in the cell nucleus. A subset of these intron retention transcripts undergoes activity-dependent splicing, cytoplasmic export, and ribosome loading, thus acutely releasing mRNAs in response to stimulation. This process requires NMDA receptor- and calmodulin-dependent kinase pathways, and it is particularly prevalent for long transcripts. We conclude that regulated intron retention in fully transcribed RNAs represents a mechanism to rapidly mobilize a pool of mRNAs in response to neuronal activity.
“Targeted Intron Retention and Excision for Rapid Gene Regulation in Response to Neuronal Activity” by Oriane Mauger, Frédéric Lemoine, and Peter Scheiffele in Neuron. Published online December 21 2016 doi:10.1016/j.neuron.2016.11.032