RNA 3′end tailing safeguards cells against products of pervasive transcription termination
Abstract Premature transcription termination yields a wealth of unadenylated (pA−) RNA. Although this can be targeted for degradation by the Nuclear EXosome Targeting (NEXT) complex, possible backup pathways remain poorly understood. Here, we find increased levels of 3′ end uridylated and adenylated...
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| Format: | Article |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54834-6 |
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| author | Guifen Wu Jérôme O. Rouvière Manfred Schmid Torben Heick Jensen |
| author_facet | Guifen Wu Jérôme O. Rouvière Manfred Schmid Torben Heick Jensen |
| author_sort | Guifen Wu |
| collection | DOAJ |
| description | Abstract Premature transcription termination yields a wealth of unadenylated (pA−) RNA. Although this can be targeted for degradation by the Nuclear EXosome Targeting (NEXT) complex, possible backup pathways remain poorly understood. Here, we find increased levels of 3′ end uridylated and adenylated RNAs upon NEXT inactivation. U-tailed RNAs are mostly short and modified by the cytoplasmic tailing enzymes, TUT4/7, following their PHAX-dependent nuclear export and prior to their degradation by the cytoplasmic exosome or the exoribonuclease DIS3L2. Longer RNAs are instead adenylated redundantly by enzymes TENT2, PAPOLA and PAPOLG. These transcripts are either degraded via the nuclear Poly(A) tail eXosome Targeting (PAXT) connection or exported and removed by the cytoplasmic exosome in a translation-dependent manner. Failure to do so decreases global translation and induces cell death. We conclude that post-transcriptional 3′ end modification and removal of excess pA− RNA is achieved by tailing enzymes and export factors shared with productive RNA pathways. |
| format | Article |
| id | doaj-art-e99415ed4c0741c4b7b9e0390f6ee14b |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e99415ed4c0741c4b7b9e0390f6ee14b2025-08-20T02:49:17ZengNature PortfolioNature Communications2041-17232024-12-0115111410.1038/s41467-024-54834-6RNA 3′end tailing safeguards cells against products of pervasive transcription terminationGuifen Wu0Jérôme O. Rouvière1Manfred Schmid2Torben Heick Jensen3Department of Molecular Biology and Genetics, Aarhus UniversityDepartment of Molecular Biology and Genetics, Aarhus UniversityDepartment of Molecular Biology and Genetics, Aarhus UniversityDepartment of Molecular Biology and Genetics, Aarhus UniversityAbstract Premature transcription termination yields a wealth of unadenylated (pA−) RNA. Although this can be targeted for degradation by the Nuclear EXosome Targeting (NEXT) complex, possible backup pathways remain poorly understood. Here, we find increased levels of 3′ end uridylated and adenylated RNAs upon NEXT inactivation. U-tailed RNAs are mostly short and modified by the cytoplasmic tailing enzymes, TUT4/7, following their PHAX-dependent nuclear export and prior to their degradation by the cytoplasmic exosome or the exoribonuclease DIS3L2. Longer RNAs are instead adenylated redundantly by enzymes TENT2, PAPOLA and PAPOLG. These transcripts are either degraded via the nuclear Poly(A) tail eXosome Targeting (PAXT) connection or exported and removed by the cytoplasmic exosome in a translation-dependent manner. Failure to do so decreases global translation and induces cell death. We conclude that post-transcriptional 3′ end modification and removal of excess pA− RNA is achieved by tailing enzymes and export factors shared with productive RNA pathways.https://doi.org/10.1038/s41467-024-54834-6 |
| spellingShingle | Guifen Wu Jérôme O. Rouvière Manfred Schmid Torben Heick Jensen RNA 3′end tailing safeguards cells against products of pervasive transcription termination Nature Communications |
| title | RNA 3′end tailing safeguards cells against products of pervasive transcription termination |
| title_full | RNA 3′end tailing safeguards cells against products of pervasive transcription termination |
| title_fullStr | RNA 3′end tailing safeguards cells against products of pervasive transcription termination |
| title_full_unstemmed | RNA 3′end tailing safeguards cells against products of pervasive transcription termination |
| title_short | RNA 3′end tailing safeguards cells against products of pervasive transcription termination |
| title_sort | rna 3 end tailing safeguards cells against products of pervasive transcription termination |
| url | https://doi.org/10.1038/s41467-024-54834-6 |
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