Back to Search
Start Over
Inflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of Aim2 .
- Source :
-
ELife [Elife] 2021 May 28; Vol. 10. Date of Electronic Publication: 2021 May 28. - Publication Year :
- 2021
-
Abstract
- 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 .<br />Competing Interests: ER, PJ, SC, MC, VS, RS, BS, RA, MJ, SC, SC No competing interests declared, MA holds options in Oxford Nanopore Technologies (ONT), is a paid consultant to ONT, received reimbursement for travel, accommodation and conference fees to speak at events organized by ONT,received research funding from ONT and is an inventor on 11 UC patents licensed to ONT (6,267,872, 6,465,193, 6,746,594, 6,936,433, 7,060,50, 8,500,982, 8,679,747, 9,481,908, 9,797,013, 10,059,988, and 10,081,835), AB received reimbursement for travel, accommodation and conference fees to speak at events organized by Oxford Nanopore Technologies (ONT)<br /> (© 2021, Robinson et al.)
- Subjects :
- 5' Untranslated Regions
Animals
Cells, Cultured
DNA-Binding Proteins metabolism
Gene Expression Profiling
Humans
Inflammation immunology
Inflammation metabolism
Macrophages immunology
Mice
Promoter Regions, Genetic
Transcriptome
Alternative Splicing
DNA-Binding Proteins genetics
Exons
Immunity, Innate genetics
Inflammation genetics
Macrophages metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 34047695
- Full Text :
- https://doi.org/10.7554/eLife.69431