Our DNA is like an encyclopaedia and genes are like the paragraphs. Like paragraphs, which are separated by spaces, our genes also contain ‘spacer DNA’, known scientifically as ‘introns’. For genes to be expressed properly, and to carry out biological functions, spacer DNA or introns need to be removed. New research from the Centenary Institute has provided novel insights into the role of these spacer DNA or introns in the development and function of monocytes and macrophages, essential components of the innate immune system.
Monocytes, white blood cells that undergo changes to become macrophages when they travel from the bloodstream into tissue, help protect the body by seeking out and destroying microbes, foreign substances and diseased cells.
Led by senior researcher Dr Justin Wong, Head of the Epigenetics and RNA Biology Program at the Centenary Institute (pictured right), the team has discovered that through a process called ‘intron retention’ by which spacer DNA are purposely maintained, monocytes and macrophages can control the expression of key genes involved in their development and critical pathogen-fighting activities.
“We discovered that these spacer sequences are deliberately retained in some cases to suppress the function of genes when they were not needed. One class of genes that are regulated this way are genes that promote the innate immune response, and control monocyte and macrophage activity. By retaining introns, partially-ready genes accumulate in the cells and await signals that pathogens are present.” said Dr Wong.
“Once an appropriate signal is detected, the spacer DNA or introns in these immune genes will be removed rapidly to reinstate their functions. Thus, there is a ‘volley’ effect to enhance the innate immune response to get rid of the pathogens quickly,” added Immanuel Green (pictured left), the lead author and a postgraduate student in Dr Wong’s lab.
Dr Wong notes that the published study provides novel insights into the molecular factors controlling vital regulators of the innate immune response system.
“Further investigation into the mechanisms that underpin this phenomenon will enable a better understanding of diseases characterised by aberrant macrophage function. Diseases include a range of vasculature, lung, body fat and kidney inflammatory pathologies,” he says.
The study, published in the journal Nucleic Acids Research, can be accessed here.
Information on Dr Wong and his research can be found here.