Evidence for targeting of CD38 mRNA by the post-transcriptional regulator protein ZFP36L1 : WestminsterResearch

Title	Evidence for targeting of CD38 mRNA by the post-transcriptional regulator protein ZFP36L1
Authors	Murphy, J.J.
Type	Conference poster
Abstract	Introduction: The ZFP36 family of post-transcriptional regulator proteins include ZFP36, ZFP36L1 and ZFP36L2. These proteins are post-transcriptional regulators of gene expression that bind to adenine uridine rich elements (AREs) in the 3’ untranslated region of mRNAs mediating RNA degradation. ZFP36L1 functions in late B cell development to negatively regulate plasma cell differentiation by targeting mRNAs of important proteins including BLIMP1 and BCL2. Previous “in silico”analysis suggested that ZFP36L1 also targeted CD38 mRNA and we report here on the results of in vitro experiments designed to test this. Materials and Methods: A 3’ luciferase reporter construct was made by cloning the CD38 ARE into the dual reporter plasmid pmirGLO. HEK293T cells were transfected with this construct together with plasmids expressing human ZFP36 proteins or mutant versions of them or control empty plasmids. 48 h later cells were harvested and Luciferase and Renilla signals were measured. Results: ZFP36L1 efficiently reduced luciferase levels compared to control constructs. This effect was not seen with a zinc finger mutant ZFP36L1 construct indicating that intact zinc fingers were required for targeting CD38 mRNA. ZFP36 and ZFP36L2 proteins also appeared capable of targeting the CD38 mRNA in these assays. siRNA mediated knockdown of endogenous ZFP36L1 protein in HeLa cells led to increased CD38 expression as measured by Western Blot analysis and immunofluorescence and flow cytometry. Conclusions: These results show that CD38 mRNA is a target for ZFP36L1 and provide further evidence for ZFP36L1 negatively regulating plasma cell differentiation by targeting mRNAs highly expressed in these cells.
Keywords	ZFP36L1
Year	2015
Conference	4th European Congress of Immunology
Web address (URL) of conference proceedings	http://www.eci-vienna2015.org/

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