Dynamic intron retention modulates gene expression in the monocytic differentiation pathway

Dynamic intron retention modulates gene expression in the monocytic differentiation pathway.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1111/imm.13435
Journal or Publication Title: Immunology
Volume: 165
Number: 2
Page Range: pp. 274-286
Date: 2022
Divisions: Epigenetics and RNA Biology
Gene and Stem Cell Therapy
Immune Imaging
Depositing User: General Admin
Identification Number: 10.1111/imm.13435
ISSN: 0019-2805
Date Deposited: 17 Mar 2022 01:43

Monocytes play a crucial role in maintaining homeostasis and mediating a successful innate immune response. They also act as central players in diverse pathological conditions, thus making them an attractive therapeutic target. Within the bone marrow, monocytes arise from a committed precursor termed Common Monocyte Progenitor (cMoP). However, molecular mechanisms that regulate the differentiation of cMoP to various monocytic subsets remain unclear. Herein, we purified murine myeloid precursors for deep poly-A-enriched RNA sequencing to understand the role of alternative splicing in the development and differentiation of monocytes under homeostasis. Our analyses revealed intron retention to be the major alternative splicing mechanism involved in the monocyte differentiation cascade, especially in the differentiation of Ly6Chi monocytes to Ly6Clo monocytes. Furthermore, we found that the intron retention of key genes involved in the differentiation of murine Ly6Chi to Ly6Clo monocytes was also conserved in humans. Our data highlight the unique role of intron retention in the regulation of the monocytic differentiation pathway.

Song, Renhua
Tikoo, Shweta
Jain, Rohit
Pinello, Natalia
Au, Amy Y. M.
Nagarajah, Rajini
Porse, Bo
Rasko, John E. J.
J.‐L. Wong, Justin
Last Modified: 17 Mar 2022 01:43
URI: https://eprints.centenary.org.au/id/eprint/1191

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