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

Turner, David J; Saveliev, Alexander; Salerno, Fiamma; Matheson, Louise S; Screen, Michael; Lawson, Hannah; Wotherspoon, David; Kranc, Kamil R et al. · Elife · 2022

basic_science · Level V

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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<sup>6</sup>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.

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