Tristetraprolin specifically regulates the expression and alternative splicing of immune response genes in Hela cells

we cloned and overexpressed human TTP-encoding gene ZFP36 in HeLa cell in the absence of inflammatory stimuli. The transcriptomes of the control and ZFP36-overexpression cells were sequenced and subjected to analysis and validation. Upon ZFP36 overexpression, expression of genes in innate immunity, including those in type I interferon signaling pathway and viral response, were specifically up-regulated, implying a transcriptional regulatory mechanism associated with the predicted DNA binding activity of TTP. TTP preferentially regulates the alternative splicing of genes involved in positive regulation of I-B/NF-B cascade and TRIF-dependent toll-like receptor signaling pathway, MAPK signaling pathway, TNF signaling pathway and T cell receptor signaling pathways.Our study indicates that TTP may regulates immune response via alternative splicing regulation and possibly by transcriptional regulation as well, which greatly expands the current understanding of the central role of TTP in regulating immune response and tumorigenesis. Tristetraprolin TTP plays a fundamental role in tumorigenesis and immunity by destabilizing target mRNAs via binding to their 3’-UTR AREs. A recent CLIP-seq study reveals that TTP binding to intronic RNA regions is enriched. TTP is also a nuclear located protein and convey putative DNA binding activity. However, it is unclear yet whether the nuclear-located TTP in the absence of stimulation regulates any gene transcription or alternative splicing of pre-mRNAs.To address these two related questions, we cloned and overexpressed human TTP-encoding gene ZFP36 in HeLa cell in the absence of inflammatory stimuli.