Pan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation
Abstract Alternative polyadenylation (APA) is a major layer of gene regulation. However, it has recently been argued that most APA represents molecular noise. To clarify their functional relevance and evolution, we quantified allele‐specific APA patterns in multiple tissues from an F1 hybrid mouse....
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2020-04-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.20199367 |
| _version_ | 1797283852696158208 |
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| author | Yisheng Li Bernhard Schaefke Xudong Zou Min Zhang Florian Heyd Wei Sun Bin Zhang Guipeng Li Weizheng Liang Yuhao He Juexiao Zhou Yunfei Li Liang Fang Yuhui Hu Wei Chen |
| author_facet | Yisheng Li Bernhard Schaefke Xudong Zou Min Zhang Florian Heyd Wei Sun Bin Zhang Guipeng Li Weizheng Liang Yuhao He Juexiao Zhou Yunfei Li Liang Fang Yuhui Hu Wei Chen |
| author_sort | Yisheng Li |
| collection | DOAJ |
| description | Abstract Alternative polyadenylation (APA) is a major layer of gene regulation. However, it has recently been argued that most APA represents molecular noise. To clarify their functional relevance and evolution, we quantified allele‐specific APA patterns in multiple tissues from an F1 hybrid mouse. We found a clearly negative correlation between gene expression and APA diversity for the 2,866 genes (24.9%) with a dominant polyadenylation site (PAS) usage above or equal to 90%, suggesting that their other PASs represent molecular errors. Among the remaining genes with multiple PASs, 3,971 genes (34.5%) express two or more isoforms with potentially functional importance. Interestingly, the genes with potentially functional minor PASs specific to neuronal tissues often express two APA isoforms with distinct subcellular localizations. Furthermore, our analysis of cis‐APA divergence shows its pattern across tissues is distinct from that of gene expression. Finally, we demonstrate that the relative usage of alternative PASs is not only affected by their cis‐regulatory elements, but also by potential coupling between transcriptional and APA regulation as well as competition kinetics between alternative sites. |
| first_indexed | 2024-03-07T17:37:49Z |
| format | Article |
| id | doaj.art-364079b8ff864a828426fadbed806a72 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T17:37:49Z |
| publishDate | 2020-04-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-364079b8ff864a828426fadbed806a722024-03-02T16:27:56ZengSpringer NatureMolecular Systems Biology1744-42922020-04-01164n/an/a10.15252/msb.20199367Pan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulationYisheng Li0Bernhard Schaefke1Xudong Zou2Min Zhang3Florian Heyd4Wei Sun5Bin Zhang6Guipeng Li7Weizheng Liang8Yuhao He9Juexiao Zhou10Yunfei Li11Liang Fang12Yuhui Hu13Wei Chen14Department of Biology Southern University of Science and Technology Shenzhen ChinaDepartment of Biology Southern University of Science and Technology Shenzhen ChinaDepartment of Biology Southern University of Science and Technology Shenzhen ChinaDepartment of Biology Southern University of Science and Technology Shenzhen ChinaLaboratory of RNA Biochemistry Institute of Chemistry and Biochemistry Freie Universität Berlin Berlin GermanyDepartment of Biology Southern University of Science and Technology Shenzhen ChinaDepartment of Biology Southern University of Science and Technology Shenzhen ChinaDepartment of Biology Southern University of Science and Technology Shenzhen ChinaDepartment of Biology Southern University of Science and Technology Shenzhen ChinaDepartment of Biology Southern University of Science and Technology Shenzhen ChinaDepartment of Biology Southern University of Science and Technology Shenzhen ChinaDepartment of Biology Southern University of Science and Technology Shenzhen ChinaDepartment of Biology Southern University of Science and Technology Shenzhen ChinaDepartment of Biology Southern University of Science and Technology Shenzhen ChinaDepartment of Biology Southern University of Science and Technology Shenzhen ChinaAbstract Alternative polyadenylation (APA) is a major layer of gene regulation. However, it has recently been argued that most APA represents molecular noise. To clarify their functional relevance and evolution, we quantified allele‐specific APA patterns in multiple tissues from an F1 hybrid mouse. We found a clearly negative correlation between gene expression and APA diversity for the 2,866 genes (24.9%) with a dominant polyadenylation site (PAS) usage above or equal to 90%, suggesting that their other PASs represent molecular errors. Among the remaining genes with multiple PASs, 3,971 genes (34.5%) express two or more isoforms with potentially functional importance. Interestingly, the genes with potentially functional minor PASs specific to neuronal tissues often express two APA isoforms with distinct subcellular localizations. Furthermore, our analysis of cis‐APA divergence shows its pattern across tissues is distinct from that of gene expression. Finally, we demonstrate that the relative usage of alternative PASs is not only affected by their cis‐regulatory elements, but also by potential coupling between transcriptional and APA regulation as well as competition kinetics between alternative sites.https://doi.org/10.15252/msb.20199367alternative polyadenylationerror hypothesisgene regulationneutral theory of molecular evolutionregulatory evolution |
| spellingShingle | Yisheng Li Bernhard Schaefke Xudong Zou Min Zhang Florian Heyd Wei Sun Bin Zhang Guipeng Li Weizheng Liang Yuhao He Juexiao Zhou Yunfei Li Liang Fang Yuhui Hu Wei Chen Pan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation Molecular Systems Biology alternative polyadenylation error hypothesis gene regulation neutral theory of molecular evolution regulatory evolution |
| title | Pan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation |
| title_full | Pan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation |
| title_fullStr | Pan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation |
| title_full_unstemmed | Pan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation |
| title_short | Pan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation |
| title_sort | pan tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation |
| topic | alternative polyadenylation error hypothesis gene regulation neutral theory of molecular evolution regulatory evolution |
| url | https://doi.org/10.15252/msb.20199367 |
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