A functional screen of RNA binding proteins identifies genes that promote or limit the accumulation of CD138+ plasma cells
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 m 6 A 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.