eCLIP identified eIF4G2 binding sites in in vitro differentiated plasma cells

Translational control plays a crucial role in the immune system, yet the key players, molecular mechanisms, and physiological functions remain poorly understood. We performed a CRISPR/Cas9-mediated screen of translation initiation factors (TIFs) and identified eukaryotic translation initiation factor 4G2 (eIF4G2) as a major regulator of internal ribosome entry site (IRES)-mediated translation during plasma cell differentiation. Mouse genetic studies confirmed the functional significance of eIF4G2 in plasma cell differentiation and antibody responses. To identify specific mRNAs whose translation initiation is regulated by eIF4G2 during plasma cell differentiation, we performed enhanced ultraviolet cross-linking immunoprecipitation coupled with high-throughput sequencing (eCLIP-seq) analysis of in vitro differentiated plasma cells.