Tumor antigen HuR binds specifically to one of five protein-binding segments in the 3 '-untranslated region of the neurofibromin messenger RNA

3'-untranslated regions of various mRNAs have been shown to contain sequenc e motifs which control mRNA stability, translatability, and efficieney of t ranslation as well as intracellular localization. We aimed to identify prot ein binding regions of the long and highly conserved 3'UTR of the mRNA codi ng for neurofibromin, a well-known tumor suppressor protein, whose genetic deficiency causes the autosomal dominant disease neurofibromatosis type 1 ( NF1). We discovered five RNA fragments that were able to undergo specific b inding to proteins from cell lysates (NF1-PBRs, NF1-protein-binding regions ). Additionally we identified the Elav-like protein HuR binding to NF1-PBR1 . HuR interacts with AU-rich elements in the 3'UTR of many protooncogenes, cytokines, and transcription factors, thereby regulating the expression of these mRNAs on the posttranscriptional level. Transfection assays with a CA T reporter construct revealed reduced expression of the reporter, suggestin g that HuR may be involved in the fine-tuning of the expression of the NF1 gene. (C) 2000 Academic Press.