Differential activity of ELAV-like RNA-binding proteins in human neuroblastoma.
Many short-lived mRNAs contain AU-rich instability elements within their 3'-untranslated region. Cellular factors that bind to these elements are thought to play a role in the regulation of mRNA degradation. In the accompanying paper (Chagnovich, D., and Cohn, S. L. (1996) J. Biol. Chem. 271, 33580-33586) we characterized the binding activity of a 40-kDa protein (p40) that interacts with high specificity with at least two AU-rich elements located within the 3'-untranslated region of N-myc. p40 activity correlates with N-myc mRNA stability in subclones of the NBL-W neuroblastoma cells line (W-N and W-S). In an effort to determine the identity of p40 we performed immunoblotting studies, immunoprecipitation experiments, and RNA gel mobility shift assays using antibodies that are directed against known RNA-binding proteins. In this paper we demonstrate that in W-N and W-S cells, p40 activity parallels the expression of embryonic letal abnormal vision (ELAV)-like proteins, and that antibodies directed against this family of RNA-binding proteins recognize p40. We also show that purified ELAV-like proteins (HuD and Hel-N1) bind with high specificity to the same N-myc 3'-untranslated region sequences as p40. Our data indicate that p40 is a member of the ELAV-like family, and suggest that this family of RNA-binding proteins may regulate N-myc mRNA turnover.
Chagnovich
D
D
Program in Tumor Cell Biology and Children's Memorial Hospital, Robert H. Lurie Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Fayos
B E
BE
Cohn
S L
SL
D051959:ELAV Proteins; D000067777:ELAV-Like Protein 2; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D051959:ELAV Proteins; D000067777:ELAV-Like Protein 2; C086811:ELAVL2 protein, human; D009419:Nerve Tissue Proteins; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins