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Status |
Public on Oct 01, 2023 |
Title |
RNA catabolism restricts ERV expression and functionalization [Iso-seq] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Endogenous retroviruses (ERVs) are remnants of ancient parasitic viral integrations and comprise a sizable portion of the genome in most organisms. Deregulated expression of ERVs in human is associated with a plethora of disease conditions, such as cancer and neurodegeneration. Epigenetic mechanisms silence most ERVs by generating a local repressive environment (heterochromatin) to prevent their expression. However, the mechanisms controlling the fate of ERVs residing in euchromatic regions of the genome (e.g. MERVL elements) are not well understood. Here, by integrating multidimensional epigenetic and genomic analyses, we demonstrate that silencing of euchromatic MERVL elements is achieved via transcription-coupled RNA degradation. Disrupting RNA catabolism promotes RNAPII elongation from MERVL promoters, increases MERVL expression and exonization, creating novel chimeric gene isoforms, and directing embryonic stem (ES) cells toward a terminal undifferentiated state. Our results indicate that RNA catabolism is a core regulatory module of gene networks that safeguards cell identity and potency, restricts MERVL functionalization and suppresses gene birth.
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Overall design |
Exosc3 cKO vs. control
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Contributor(s) |
Torre D, Fstkchyan Y, Marazzi I |
Citation missing |
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Submission date |
May 31, 2022 |
Last update date |
Oct 13, 2023 |
Contact name |
Robert Sebra |
E-mail(s) |
robert.sebra@mssm.edu
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Organization name |
Icahn School of Medicine at Mount Sinai
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Street address |
1 Gustave L. Levy Place
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City |
New York |
State/province |
New York |
ZIP/Postal code |
10029 |
Country |
USA |
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Platforms (1) |
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Samples (8)
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This SubSeries is part of SuperSeries: |
GSE205211 |
RNA catabolism restricts ERV expression and functionalization |
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Relations |
BioProject |
PRJNA844040 |