Inflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of Aim2
Determining the layers of gene regulation within the innate immune response is critical to our understanding of the cellular responses to infection and dysregulation in disease. We identified a conserved mechanism of gene regulation in human and mouse via changes in alternative first exon (AFE) usag...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/69431 |
| _version_ | 1811199406783856640 |
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| author | Elektra K Robinson Pratibha Jagannatha Sergio Covarrubias Matthew Cattle Valeriya Smaliy Rojin Safavi Barbara Shapleigh Robin Abu-Shumays Miten Jain Suzanne M Cloonan Mark Akeson Angela N Brooks Susan Carpenter |
| author_facet | Elektra K Robinson Pratibha Jagannatha Sergio Covarrubias Matthew Cattle Valeriya Smaliy Rojin Safavi Barbara Shapleigh Robin Abu-Shumays Miten Jain Suzanne M Cloonan Mark Akeson Angela N Brooks Susan Carpenter |
| author_sort | Elektra K Robinson |
| collection | DOAJ |
| description | Determining the layers of gene regulation within the innate immune response is critical to our understanding of the cellular responses to infection and dysregulation in disease. We identified a conserved mechanism of gene regulation in human and mouse via changes in alternative first exon (AFE) usage following inflammation, resulting in changes to the isoforms produced. Of these AFE events, we identified 95 unannotated transcription start sites in mice using a de novo transcriptome generated by long-read native RNA-sequencing, one of which is in the cytosolic receptor for dsDNA and known inflammatory inducible gene, Aim2. We show that this unannotated AFE isoform of Aim2 is the predominant isoform expressed during inflammation and contains an iron-responsive element in its 5′UTR enabling mRNA translation to be regulated by iron levels. This work highlights the importance of examining alternative isoform changes and translational regulation in the innate immune response and uncovers novel regulatory mechanisms of Aim2. |
| first_indexed | 2024-04-12T01:48:25Z |
| format | Article |
| id | doaj.art-7623ad82df924ce0aad8a2be411d8d62 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:48:25Z |
| publishDate | 2021-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7623ad82df924ce0aad8a2be411d8d622022-12-22T03:53:01ZengeLife Sciences Publications LtdeLife2050-084X2021-05-011010.7554/eLife.69431Inflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of Aim2Elektra K Robinson0https://orcid.org/0000-0003-1427-3897Pratibha Jagannatha1https://orcid.org/0000-0003-0257-3139Sergio Covarrubias2Matthew Cattle3Valeriya Smaliy4Rojin Safavi5Barbara Shapleigh6Robin Abu-Shumays7Miten Jain8Suzanne M Cloonan9Mark Akeson10Angela N Brooks11https://orcid.org/0000-0002-7898-3073Susan Carpenter12https://orcid.org/0000-0002-5600-5404Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, United StatesDepartment of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, United States; Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, United StatesDepartment of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, United StatesDepartment of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, United StatesDepartment of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, United StatesDepartment of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, United StatesDepartment of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, United StatesDepartment of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, United StatesDepartment of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, United StatesDivision of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, United StatesDepartment of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, United StatesDepartment of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, United StatesDepartment of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, United StatesDetermining the layers of gene regulation within the innate immune response is critical to our understanding of the cellular responses to infection and dysregulation in disease. We identified a conserved mechanism of gene regulation in human and mouse via changes in alternative first exon (AFE) usage following inflammation, resulting in changes to the isoforms produced. Of these AFE events, we identified 95 unannotated transcription start sites in mice using a de novo transcriptome generated by long-read native RNA-sequencing, one of which is in the cytosolic receptor for dsDNA and known inflammatory inducible gene, Aim2. We show that this unannotated AFE isoform of Aim2 is the predominant isoform expressed during inflammation and contains an iron-responsive element in its 5′UTR enabling mRNA translation to be regulated by iron levels. This work highlights the importance of examining alternative isoform changes and translational regulation in the innate immune response and uncovers novel regulatory mechanisms of Aim2.https://elifesciences.org/articles/69431Macrophagessplicinghuman |
| spellingShingle | Elektra K Robinson Pratibha Jagannatha Sergio Covarrubias Matthew Cattle Valeriya Smaliy Rojin Safavi Barbara Shapleigh Robin Abu-Shumays Miten Jain Suzanne M Cloonan Mark Akeson Angela N Brooks Susan Carpenter Inflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of Aim2 eLife Macrophages splicing human |
| title | Inflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of Aim2 |
| title_full | Inflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of Aim2 |
| title_fullStr | Inflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of Aim2 |
| title_full_unstemmed | Inflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of Aim2 |
| title_short | Inflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of Aim2 |
| title_sort | inflammation drives alternative first exon usage to regulate immune genes including a novel iron regulated isoform of aim2 |
| topic | Macrophages splicing human |
| url | https://elifesciences.org/articles/69431 |
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