HuD, a neuronal-specific RNA-binding protein, is a putative regulator of N-myc pre-mRNA processing/stability in malignant human neuroblasts.
N-myc gene copy numbers and transcription rates are similar in N (neuroblastic, tumorigenic) and S (non-neuronal, non-tumorigenic) neuroblastoma cells with chromosomally integrated amplified N-myc genes. However, N cells show significantly higher N-myc mRNA levels than S cells. Therefore, post-transcriptional control of N-myc gene expression must differ between these cell types. Since no differences in N-myc mRNA half-life were found between N and S cells from two cell lines, steady-state levels of N-myc pre-mRNA processing intermediates were analysed. Results suggest that the differences in N-myc expression arise primarily at the nuclear post-transcriptional level. The neuronal-specific RNA-binding Hu proteins are present in cytoplasmic and nuclear fractions of N cells and one of them, HuD, binds specifically to both exonic and intronic N-myc RNA sequences. In sense and antisense HuD-transfected N cells, there are coordinate changes in HuD and N-myc expression levels. Thus, we propose that HuD plays a role in the nuclear processing/stability of N-myc pre-mRNA in N-type neuroblastoma cells.
Lazarova
D L
DL
Department of Biological Sciences, Fordham University, Bronx, New York 10458, USA.
Spengler
B A
BA
Biedler
J L
JL
Ross
R A
RA
D002460:Cell Line; D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; D006207:Half-Life; D006801:Humans; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D016372:RNA, Antisense; D016601:RNA-Binding Proteins / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; C498010:ELAVL4 protein, human; D009419:Nerve Tissue Proteins; D016271:Proto-Oncogene Proteins c-myc; D016372:RNA, Antisense; D016601:RNA-Binding Proteins