4 research outputs found
Macrophage development and activation involve coordinated intron retention in key inflammatory regulators
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