Integrated genomic analysis reveals key features of long undecoded transcript isoform-based gene repression
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved..
Long undecoded transcript isoforms (LUTIs) represent a class of non-canonical mRNAs that downregulate gene expression through the combined act of transcriptional and translational repression. While single gene studies revealed important aspects of LUTI-based repression, how these features affect gene regulation on a global scale is unknown. Using transcript leader and direct RNA sequencing, here, we identify 74 LUTI candidates that are specifically induced in meiotic prophase. Translational repression of these candidates appears to be ubiquitous and is dependent on upstream open reading frames. However, LUTI-based transcriptional repression is variable. In only 50% of the cases, LUTI transcription causes downregulation of the protein-coding transcript isoform. Higher LUTI expression, enrichment of histone 3 lysine 36 trimethylation, and changes in nucleosome position are the strongest predictors of LUTI-based transcriptional repression. We conclude that LUTIs downregulate gene expression in a manner that integrates translational repression, chromatin state changes, and the magnitude of LUTI expression.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:81 |
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| Enthalten in: |
Molecular cell - 81(2021), 10 vom: 20. Mai, Seite 2231-2245.e11 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tresenrider, Amy [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.06.2021 Date Revised 16.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.molcel.2021.03.013 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Long undecoded transcript isoforms (LUTIs) represent a class of non-canonical mRNAs that downregulate gene expression through the combined act of transcriptional and translational repression. While single gene studies revealed important aspects of LUTI-based repression, how these features affect gene regulation on a global scale is unknown. Using transcript leader and direct RNA sequencing, here, we identify 74 LUTI candidates that are specifically induced in meiotic prophase. Translational repression of these candidates appears to be ubiquitous and is dependent on upstream open reading frames. However, LUTI-based transcriptional repression is variable. In only 50% of the cases, LUTI transcription causes downregulation of the protein-coding transcript isoform. Higher LUTI expression, enrichment of histone 3 lysine 36 trimethylation, and changes in nucleosome position are the strongest predictors of LUTI-based transcriptional repression. We conclude that LUTIs downregulate gene expression in a manner that integrates translational repression, chromatin state changes, and the magnitude of LUTI expression | ||
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| 700 | 1 | |a Morse, Kaitlin |e verfasserin |4 aut | |
| 700 | 1 | |a Jorgensen, Victoria |e verfasserin |4 aut | |
| 700 | 1 | |a Chia, Minghao |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Hanna |e verfasserin |4 aut | |
| 700 | 1 | |a van Werven, Folkert Jacobus |e verfasserin |4 aut | |
| 700 | 1 | |a Ünal, Elçin |e verfasserin |4 aut | |
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