期刊
NUCLEIC ACIDS RESEARCH
卷 48, 期 12, 页码 6513-6529出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa435
关键词
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资金
- National Health and Medical Research Council [1128175, 1129901, 1126306, 1063559]
- Cancer Council of NSW [20-12]
- NSW Genomics Collaborative Grant
- Cure the Future
- Cancer Institute of New South Wales
- Australian Government Research Training Program PhD Scholarships
- Sydney Catalyst Postgraduate Scholarship
- NHMRC Postgraduate Scholarship
- Arrow Bone Marrow Transplant Foundation Supplementary PhD Scholarship
- National Health and Medical Research Council of Australia [1126306, 1128175, 1129901, 1063559] Funding Source: NHMRC
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 pro-inflammatory stimuli, intron-retaining CXCL2 and NFK-BIZ 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.
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