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 sequence motifs which control mRNA stability, translatability, and efficiency of translation as well as intracellular localization. We aimed to identify protein binding regions of the long and highly conserved 3'UTR of the mRNA coding 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 binding 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 CAT reporter construct revealed reduced expression of the reporter, suggesting that HuR may be involved in the fine-tuning of the expression of the NF1 gene.
Haeussler
J
J
Department of Human Genetics, Department of Medical Genetics, University of Ulm, Albert-Einstein-Allee 11, Ulm, D-89081, Germany.
Haeusler
J
J
Striebel
A M
AM
Assum
G
G
Vogel
W
W
Furneaux
H
H
Krone
W
W
D020413:3' Untranslated Regions / Q000737:chemistry / Q000378:metabolism*; D000954:Antigens, Surface; D001665:Binding Sites; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics; D025542:Neurofibromin 1; D016366:Open Reading Frames; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D020413:3' Untranslated Regions; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D009419:Nerve Tissue Proteins; D025542:Neurofibromin 1; D011506:Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015500:Chloramphenicol O-Acetyltransferase