HuD, a neuronal-specific RNA-binding protein, is a potential regulator of MYCN expression in human neuroblastoma cells.

Abstract

HuD is one of a family of neural antigens recognised by the sera of patients with antibody-associated paraneoplastic encephalomyelitis. Localised exclusively to neurons, these proteins are among the earliest markers of the developing nervous system. Sequence analysis suggests that HuD is an RNA-binding protein. Hu protein levels were determined for the three cell types characterising human neuroblastoma cell lines: sympathoadrenal neuroblasts (N), substrate-adherent Schwann/glial/melanoblastic precursors (S) and stem cells (I) which can give rise to both N and S cells. Western blot analysis showed similar levels of protein in three N-type cell lines; S cells have no detectable Hu protein. Northern blot analysis indicated that N cells express all three Hu genes, HuD, HuC and Hel-N1. N cells, mostly from MYCN-amplified cell lines, have consistently higher steady-state levels of MYCN mRNA than S cell counterparts. Nuclear run-on and mRNA half-life experiments revealed no differences in transcription rate or mRNA stability between N and S cells from the LA-N-1 cell line, implicating differences in post-transcriptional regulation. HuD is postulated to be instrumental in splicing/processing and/or stabilisation of mRNAs involved in cell growth and neuronal differentiation. As determined by gel-mobility shift assays, HuD fusion protein binds to the 3'UTR of human MYCN mRNA. Analysis of HuD deletion mutants has demonstrated that the first and second RNA-recognition motifs (RRMs) are required for binding. Whether HuD regulates MYCN expression and thereby influences tumour aggressiveness is of major interest.

• Authors: R A Ross, D L Lazarova, G T Manley, P S Smitt, B A Spengler, J B Posner, J L Biedler
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 33 Issue 12 Pg. 2071-4 (Oct 1997) ISSN: 0959-8049 [Print] England
• PMID: 9516855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ELAV Proteins
• ELAV-Like Protein 4
• ELAVL4 protein, human
• Neoplasm Proteins
• Nerve Tissue Proteins
• Proto-Oncogene Proteins c-myc
• RNA, Messenger
• RNA-Binding Proteins

Topics

• Binding Sites
• Blotting, Northern
• ELAV Proteins
• ELAV-Like Protein 4
• Humans
• Neoplasm Proteins (genetics, metabolism, physiology)
• Nerve Tissue Proteins
• Neuroblastoma (metabolism, pathology)
• Protein Binding
• Proto-Oncogene Proteins c-myc (genetics, metabolism, physiology)
• RNA, Messenger (metabolism)
• RNA-Binding Proteins (genetics, metabolism, physiology)
• Sequence Deletion
• Tumor Cells, Cultured