ZFP36L2-mRNA Interaction: Drawing general rules based on transcriptomic analysis

In this study we focus on identifying potential physiological targets of ZFP36L2 (Zinc finger protein like 2 or L2), one of the three primate members of the ZFP36 protein family. Most studies on ARE specificity of this small family were conducted using the prototypical family member, ZFP36 or TTP; however, less is known about the other family member's specificity. Previous studies of ZFP36L2 target mRNAs identified a high proportion of transcription factors in two different systems, cells from the erythrocyte lineage and oocytes. However, there is minimal overlap between the genes identified in these studies and those identified here using mouse spleens lacking ZFP36L2 (L2-cKO). This observation suggests that ZFP36L2 targeting is occurring in a highly tissue specific manner. Aiming to understand what factors govern this potential tissue specificity, we characterized the differentially expressed genes in our L2-cKO mouse model in the spleen, an organ that expresses L2 at high levels in humans and mice. We performed transcriptome-wide analysis in RNA spleen samples from mice lacking ZFP36L2 (L2-cKO) and normally expressing (WT). Differential gene expression (DEG) of WT vs. L2-cKO spleens revealed 549 up regulated and 603 down regulated genes. Nine genes were validated in qPCR assays. Overall design: Adenine-uridine rich element-RNA-binding proteins (ARE-RBP) generally either stabilize or destabilize the target transcripts they bind. A remaining challenge in the field is understanding the specificity of targeting by ARE-RBPs and how this dictates function. We performed transcriptome-wide analysis in RNA spleen samples from mice lacking ZFP36L2 (L2-cKO) and normally expressing (WT).