3T3-L1 preadipocytes ectopically expressing the mammalian RNA-binding protein Hel-N1 expressed up to 10-fold more glucose transporter (GLUT1) protein and exhibited elevated rates of basal glucose uptake. Hel-N1 is a member of the ELAV-like family of proteins associated with the induction and maintenance of differentiation in various species. ELAV proteins are known to bind in vitro to short stretches of uridylates in the 3 untranslated regions (3 UTRs) of unstable mRNAs encoding growth-regulatory proteins involved in transcription and signal transduction. GLUT1 mRNA also contains a large 3 UTR with a U-rich region that binds specifically to Hel-N1 in vitro. Analysis of the altered GLUT1 expression at the translational and posttranscriptional levels suggested a mechanism involving both mRNA stabilization and accelerated formation of translation initiation complexes. These findings are consistent with the hypothesis that the Hel-N1 family of proteins modulate gene expression at the level of mRNA in the cytoplasm.Interaction of RNA-binding proteins with cis elements in mRNAs is believed to be involved in regulation of their stability and translational efficiency (reviewed in reference 32). The regulated stability of transferrin, granulocyte-macrophage colony-stimulating factor, and histone mRNAs has been shown, at least in part, to be controlled by the binding of specific proteins to consensus sequences in the 3Ј untranslated region (3ЈUTR) of these messages (3, 37, 41). Studies of tobacco mosaic virus, the Drosophila melanogaster developmental gene hunchback, human cytokine, and 15-lipoxygenase mRNAs have demonstrated that the 3ЈUTR also contains information capable of regulating translational efficiency which may be mediated by RNA-binding proteins (13,25,35,36). A major class of RNA-binding proteins which possess an 80-amino-acid consensus element, termed the RNA recognition motif (RRM) (39), which forms the core of a functional RNAbinding domain has been identified.Hel-N1 (human embryonic lethal abnormal vision [ELAV]-like neuronal protein 1), a mammalian homolog of Drosophila ELAV, is an mRNA-binding protein of the RRM family (15,16,27). Recent studies on Hel-N1, and the alternative form, Hel-N2 (lacking a 13-amino-acid segment between RRM2 and RRM3), in human medulloblastoma cells and embryonic carcinoma P19 cells have indicated that it plays a role in mRNA metabolism (15). These proteins are bound to poly(A) ϩ mRNA in granular RNP structures, and their expression is upregulated during neuronal cell differentiation of P19 cells (15). Likewise, hNT2 cells when induced to differentiate by retinoic acid exhibited a marked increase in the expression of human ELAV-like proteins which colocalized with mRNPs associated with polysomes (1). Hence, data from both of these studies support an important role for mammalian ELAV-like proteins in the processes of cell growth and differentiation.Interestingly, members of the ELAV family have been shown to bind the AU-rich regions of the 3ЈUTRs in cytokine and proto-oncogene m...