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Published on: May 23, 2013
Imprinted Maternally Expressed microRNAs Antagonize Paternally Driven Gene Programs in Neurons
Amanda J Whipple1, Vincent Breton-Provencher2, Hannah N Jacobs3
1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Maternally expressed microRNAs (miRNAs) from the miR-379/410 cluster regulate neuronal gene expression. Deleting this cluster impacts synaptic transmission and neuronal function by altering target gene activity.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- Genomic imprinting regulates parent-specific gene expression.
- MicroRNAs (miRNAs) are key post-transcriptional regulators.
- Imprinted genes are often co-regulated in biological pathways.
Purpose of the Study:
- To functionally characterize the imprinted miR-379/410 miRNA cluster.
- To investigate the consequences of maternally expressed miRNAs in neurons.
- To explore miRNA-mediated antagonism of paternally expressed genes.
Main Methods:
- Utilized an induced neuron (iN) culture system.
- Performed maternal deletion of the miR-379/410 miRNA cluster.
- Analyzed target gene expression and protein levels via RNA-induced silencing complex (RISC) interactions.
Main Results:
- Maternally expressed miRNAs target transcriptional and developmental regulators, including Plagl1.
- Maternal deletion led to increased target protein levels and altered transcriptional programs.
- Upregulation of synaptic transmission and neuronal function pathways observed.
- De-repression of Plagl1 partially explains observed transcriptional changes.
Conclusions:
- Maternally expressed miRNAs from the miR-379/410 cluster play a critical role in neuronal development and function.
- These miRNAs antagonize paternally expressed gene programs in neurons.
- Imprinted miRNA clusters contribute to the complexity of gene regulation in the brain.
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