Imprinted Maternally Expressed microRNAs Antagonize Paternally Driven Gene Programs in Neurons
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 an...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/130445 |
| _version_ | 1826195406586904576 |
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| author | Whipple, Amanda Joy Breton-Provencher, Vincent Sur, Mriganka Sharp, Phillip A. |
| author2 | Picower Institute for Learning and Memory |
| author_facet | Picower Institute for Learning and Memory Whipple, Amanda Joy Breton-Provencher, Vincent Sur, Mriganka Sharp, Phillip A. |
| author_sort | Whipple, Amanda Joy |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:12:09Z |
| format | Article |
| id | mit-1721.1/130445 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:12:09Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1304452021-09-20T19:07:00Z Imprinted Maternally Expressed microRNAs Antagonize Paternally Driven Gene Programs in Neurons Whipple, Amanda Joy Breton-Provencher, Vincent Sur, Mriganka Sharp, Phillip A. Picower Institute for Learning and Memory Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Koch Institute for Integrative Cancer Research at MIT 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. National Institutes of Health (U.S.) (Grants P01-CA042063, R01-GM034277, R01-CA133404, R01-EY007023, R01-EY028219, R01-NS090473) National Cancer Institute (U.S.) (Grant P30-CA14051) National Institutes of Health (U.S.) (Postdoctoral fellowships NIH F32HD090833) National Institutes of Health (U.S.) (Grant FRQS 31677) Natural Sciences and Engineering Research Council Canada (Grant PDF-48724-2016) 2021-04-12T14:49:49Z 2021-04-12T14:49:49Z 2020-04 2019-12 2021-04-06T15:23:07Z Article http://purl.org/eprint/type/JournalArticle 1097-2765 https://hdl.handle.net/1721.1/130445 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) en 10.1016/J.MOLCEL.2020.01.020 Molecular Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Whipple, Amanda Joy Breton-Provencher, Vincent Sur, Mriganka Sharp, Phillip A. Imprinted Maternally Expressed microRNAs Antagonize Paternally Driven Gene Programs in Neurons |
| title | Imprinted Maternally Expressed microRNAs Antagonize Paternally Driven Gene Programs in Neurons |
| title_full | Imprinted Maternally Expressed microRNAs Antagonize Paternally Driven Gene Programs in Neurons |
| title_fullStr | Imprinted Maternally Expressed microRNAs Antagonize Paternally Driven Gene Programs in Neurons |
| title_full_unstemmed | Imprinted Maternally Expressed microRNAs Antagonize Paternally Driven Gene Programs in Neurons |
| title_short | Imprinted Maternally Expressed microRNAs Antagonize Paternally Driven Gene Programs in Neurons |
| title_sort | imprinted maternally expressed micrornas antagonize paternally driven gene programs in neurons |
| url | https://hdl.handle.net/1721.1/130445 |
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