Abstract POST-TRANSCRIPTIONAL REGULATION OF mRNA METABOLISM DURING DIFFERENTIATION OF 3T3-L1 CELLS: ROLE OF HuR

Our studies address early control points in the differentiation process that are necessary for expression as well as the maintenance of the adipocyte phenotype. We have focused on the post-transcriptional regulation of mRNA metabolism by the RNA binding protein HuR. Depending on the particular mRNA, HuR has been suggested to control polyadenylation, translocation to the cytosol, mRNA stability, and/or translational efficiency. Using the 3T3-L1 preadipocyte cell line, we have demonstrated a critical role for HuR in the differentiation process by use of siRNA mediated suppression which resulted in an inhibition of differentiation. We have identified several mRNAs that serve as HuR ligands early in the differentiation process, one of which is C/EBPβ, an important adipocyte transcription factor, whose expression is highly controlled and essential for proper acquisition of the adipocyte phenotype. Within minutes of induction of differentiation, HuR forms an mRNP complex with C/EBPβ mRNA in the nucleus followed by translocation to the cytoplasm. HuR remains associated with C/EBPβ mRNA suggesting a role in mRNA stability and translation efficiency. Our data suggest that formation of this complex in the nucleu