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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	Macrophages splicing human Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7623ad82df924ce0aad8a2be411d8d62
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spelling	oai:doaj.org-article:7623ad82df924ce0aad8a2be411d8d622021-11-29T12:12:44ZInflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of Aim210.7554/eLife.694312050-084Xe69431https://doaj.org/article/7623ad82df924ce0aad8a2be411d8d622021-05-01T00:00:00Zhttps://elifesciences.org/articles/69431https://doaj.org/toc/2050-084XDetermining 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.Elektra K RobinsonPratibha JagannathaSergio CovarrubiasMatthew CattleValeriya SmaliyRojin SafaviBarbara ShapleighRobin Abu-ShumaysMiten JainSuzanne M CloonanMark AkesonAngela N BrooksSusan CarpentereLife Sciences Publications LtdarticleMacrophagessplicinghumanMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Macrophages splicing human Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	Macrophages splicing human Medicine R Science Q Biology (General) QH301-705.5 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
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.
format	article
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
title	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_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_sort	inflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of aim2
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/7623ad82df924ce0aad8a2be411d8d62
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Inflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of Aim2

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