ZFP36L1 Regulates the mRNA Expression of MAPK Phoshatase-1 and Other Immediate-Early Genes during the Early Stage of Adipogenesis
Date Issued
2010
Date
2010
Author(s)
Lin, Tzi-Yang
Abstract
Immediate-early genes (IEGs) are expressed instantly after the trigger of 3T3L1 preadipocyte differentiation and are under tight controls at transcriptional and post-transcriptional levels. The mechanisms underlying the rapid clearance of IEG mRNAs are of our interest. Our previous studies have revealed that Tristetraprolin (TTP), a RNA binding protein, recognized and destabilized MAP kinase phosphatase-1 (MKP-1) mRNAs through a mechanism called Adenyl/Uracil-rich (AU-rich) elements-mediated mRNA decay (AMD). However, the functions of other members in TTP protein family are not well-characterized in adipogenesis. In this study, we showed that ZFP36L1, another TTP family member, played roles in cell proliferation and post-transcriptional gene regulation in adipogenesis. In contrast to the inducible-property of TTP, ZFP36L1 protein was biphasically expressed within the first hour after induction and the expression of MKP-1 mRNA was reciprocal to the protein dynamics of ZFP36L1. This unusual protein dynamics was achieved by translational repression rather than by the change of ZFP36L1 protein stability. Importantly, the MKP-1 mRNA-binding and destabilizing abilities of ZFP36L1 were comparable to TTP and knockdown of ZFP36L1 in 3T3-L1 cells resulted in an upsurge of MKP-1 mRNA. Moreover, ZFP36L1 underwent a significant phosphorylation by ERK signaling immediately after induction and the phosphorylation status seemed to have some effects on its mRNA destabilizing ability. Finally, the effect of ZFP36L1 on the whole process of adipogenesis was investigated. This study elucidates a possible role of ZFP36L1 in adipogenesis and indicates that 3T3-L1 differentiating cells accomplish an elaborate regulation of MKP-1 mRNA expression by coordinating ZFP36L1 and TTP protein dynamics.
Subjects
Adipocytes differentiation
AU-rich elements
ARE-mediated mRNA decay (AMD)
immediate-early genes
post-translational modifications
Type
thesis
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