A functional screen of RNA binding proteins identifies genes that promote or limit the accumulation of CD138+ plasma cells

RNA 结合蛋白的功能筛选可识别促进或限制 CD138+ 浆细胞积累的基因

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作者:David J Turner, Alexander Saveliev, Fiamma Salerno, Louise S Matheson, Michael Screen, Hannah Lawson, David Wotherspoon, Kamil R Kranc, Martin Turner

Abstract

To identify roles of RNA binding proteins (RBPs) in the differentiation or survival of antibody secreting plasma cells we performed a CRISPR/Cas9 knockout screen of 1213 mouse RBPs for their ability to affect proliferation and/or survival, and the abundance of differentiated CD138 + cells in vitro. We validated the binding partners CSDE1 and STRAP as well as the m6A binding protein YTHDF2 as promoting the accumulation of CD138 + cells in vitro. We validated the EIF3 subunits EIF3K and EIF3L and components of the CCR4-NOT complex as inhibitors of CD138 + cell accumulation in vitro. In chimeric mouse models YTHDF2-deficient plasma cells failed to accumulate.

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