Imprinted Maternally Expressed microRNAs Antagonize Paternally Driven Gene Programs in Neurons
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nihms-1569187.pdf
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Accepted version
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Author(s)
Whipple, Amanda Joy
Breton-Provencher, Vincent
Jacobs, Hannah N.
Patra, Chitta Ranjan
Sur, Mriganka
Sharp, Phillip A.
Date Issued
April 2020
Journal
Molecular Cell
Publisher
Elsevier BV
Citation
Whipple, Amanda J. et al. “Imprinted Maternally Expressed microRNAs Antagonize Paternally Driven Gene Programs in Neurons.” Molecular Cell, 78, 1 (April 2020): 85–95.e8 © 2020 The Author(s)
Version
Author's final manuscript
Abstract
Imprinted genes with parental-biased allelic expression are frequently co-regulated and enriched in common biological pathways. Here, we functionally characterize a large cluster of microRNAs (miRNAs) expressed from the maternally inherited allele (“maternally expressed”) to explore the molecular and cellular consequences of imprinted miRNA activity. Using an induced neuron (iN) culture system, we show that maternally expressed miRNAs from the miR-379/410 cluster direct the RNA-induced silencing complex (RISC) to transcriptional and developmental regulators, including paternally expressed transcripts like Plagl1. Maternal deletion of this imprinted miRNA cluster resulted in increased protein levels of several targets and upregulation of a broader transcriptional program regulating synaptic transmission and neuronal function. A subset of the transcriptional changes resulting from miR-379/410 deletion can be attributed to de-repression of Plagl1. These data suggest maternally expressed miRNAs antagonize paternally driven gene programs in neurons.
MIT Department
Picower Institute for Learning and Memory
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.MOLCEL.2020.01.020
