@article{937c51b9517b446798074305282849c3,
title = "Quaking promotes monocyte differentiation into pro-atherogenic macrophages by controlling pre-mRNA splicing and gene expression",
abstract = "A hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to induce transcriptional changes associated with macrophage phenotype, but posttranscriptional control of human macrophage differentiation is less well understood. Here we show that expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes and early human atherosclerotic lesions, but are abundant in macrophages of advanced plaques. Depletion of QKI protein impairs monocyte adhesion, migration, differentiation into macrophages and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, reveal striking changes in QKI-dependent messenger RNA levels and splicing of RNA transcripts. The biological importance of these transcripts and requirement for QKI during differentiation illustrates a central role for QKI in posttranscriptionally guiding macrophage identity and function.",
author = "{De Bruin}, {Ruben G.} and Lily Shiue and Jurri{\"e}n Prins and {De Boer}, {Hetty C.} and Anjana Singh and Fagg, {W. Samuel} and {Van Gils}, {Janine M.} and Duijs, {Jacques M.G.J.} and Sol Katzman and Kraaijeveld, {Adriaan O.} and Stefan B{\"o}hringer and Leung, {Wai Y.} and Kielbasa, {Szymon M.} and Donahue, {John P.} and {Van Der Zande}, {Patrick H.J.} and Rick Sijbom and {Van Alem}, {Carla M.A.} and Ilze Bot and {Van Kooten}, Cees and Jukema, {J. Wouter} and {Van Esch}, Hilde and Rabelink, {Ton J.} and Hilal Kazan and Biessen, {Erik A.L.} and Manuel Ares and {Van Zonneveld}, {Anton Jan} and {Van Der Veer}, {Eric P.}",
note = "Funding Information: For the studies described in this manuscript, we greatly appreciate the participation and cooperation of the QKI haploinsufficient patient and her family members. R.G.d.B. and E.P.v.d.V. were supported by Netherlands Institute for Regenerative Medicine research grants (Grant No. FES0908). This research was also made possible by a private research endowment to E.P.v.d.V. L.S., S.K., J.P.D. and M.A.J. were supported by US National Institutes of Health grant GM040478 and W.S.F. was supported by training grants CIRM TG2-01157 and NIH T32 GM008646. H.K. was supported by European Union Marie Curie CIG grant (PTRCODE) and TUBITAK grant (113E159). We also gratefully acknowledge Dr Christopher Burge and his laboratory at the Massachusetts Institute of Technology, for assistance with the generation of sashimi plots from our RNA-seq data. In addition, we acknowledge Dr Arnoud Sonneberg at the Netherlands Cancer Institute for the in-depth discussions and integrin antibodies.",
year = "2016",
month = mar,
day = "31",
doi = "10.1038/ncomms10846",
language = "English (US)",
volume = "7",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}