Macrophage development and activation involve coordinated intron retention in key inflammatory regulators

Macrophage development and activation involve coordinated intron retention in key inflammatory regulators.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1093/nar%2Fgkaa435
Journal or Publication Title: Nucleic Acids Research
Volume: 48
Number: 12
Page Range: pp. 6513-6529
Date: 2020
Divisions: Computational BioMedicine
Epigenetics and RNA Biology
Gene and Stem Cell Therapy
Immune Imaging
Depositing User: General Admin
Identification Number: 10.1093/nar/gkaa435
ISSN: 0305-1048
Date Deposited: 04 Jan 2021 02:47
Abstract:

Monocytes and macrophages are essential components of the innate immune system. Herein, we report that intron retention (IR) plays an important role in the development and function of these cells. Using Illumina mRNA sequencing, Nanopore direct cDNA sequencing and proteomics analysis, we identify IR events that affect the expression of key genes/proteins involved in macrophage development and function. We demonstrate that decreased IR in nuclear-detained mRNA is coupled with increased expression of genes encoding regulators of macrophage transcription, phagocytosis and inflammatory signalling, including ID2, IRF7, ENG and LAT. We further show that this dynamic IR program persists during the polarisation of resting macrophages into activated macrophages. In the presence of proinflammatory stimuli, intron-retaining CXCL2 and NFKBIZ transcripts are rapidly spliced, enabling timely expression of these key inflammatory regulators by macrophages. Our study provides novel insights into the molecular factors controlling vital regulators of the innate immune response.

Creators:
Creators
Email
Wong, Justin J-L
UNSPECIFIED
Rasko, John E J
UNSPECIFIED
Hayashi, Rippei
UNSPECIFIED
Larance, Mark
UNSPECIFIED
Schmitz, Ulf
UNSPECIFIED
Roediger, Ben
UNSPECIFIED
Clark, Susan J
UNSPECIFIED
Nair, Shalima S
UNSPECIFIED
Wong, Alex C H
UNSPECIFIED
Kwok, Chau-To
UNSPECIFIED
Halstead, James M
UNSPECIFIED
Lee, Quintin
UNSPECIFIED
Song, Renhua
UNSPECIFIED
Pinello, Natalia
UNSPECIFIED
Green, Immanuel D
UNSPECIFIED
Last Modified: 04 Jan 2021 02:47
URI: https://eprints.centenary.org.au/id/eprint/764

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