DEK is a possible IgM mRNA processing regulator

Abstract

The IgM pre‐mRNA is alternatively processed to two mRNAs that encode secreted or membrane‐associated proteins, through competing splice and cleavage‐polyadenylation reactions. The relative use of the competing reactions changes during B cell development and it is the architecture of the gene rather than specific regulatory elements that are required for this regulation. To identify potential trans‐regulators of IgM, we analysed RNA from a mouse B cell line before and after stimulation with LPS or IL‐5 to induce maturation. One of the genes identified to change is DEK, which encodes an abundant nuclear protein involved in several cellular processes, including mRNA splicing. We confirmed that DEK expression is higher in several mouse B cell lines than plasma cell lines by RT‐qPCR, consistent with the microarray data. Western blot analysis also suggests that DEK protein levels are higher in B cells compared to plasma cells. If DEK contributes to IgM mRNA processing regulation, we expect that overexpression of DEK in a plasma cell line would decrease the pA/splice expression ratio. Conversely, decreasing DEK levels in B cells by siRNA may increase this ratio. Whether the effect of DEK is direct or indirect will be assessed by ChIP assay. We are also examining other potential regulators from the microarray data to better understand IgM mRNA processing regulation. Supported by NSF grant MCB‐0919099.