Hel-N1: an autoimmune RNA-binding protein with specificity for 3' uridylate-rich untranslated regions of growth factor mRNAs.

Abstract

We have investigated the RNA binding specificity of Hel-N1, a human neuron-specific RNA-binding protein, which contains three RNA recognition motifs. Hel-N1 is a human homolog of Drosophila melanogaster elav, which plays a vital role in the development of neurons. A random RNA selection procedure revealed that Hel-N1 prefers to bind RNAs containing short stretches of uridylates similar to those found in the 3' untranslated regions (3' UTRs) of oncoprotein and cytokine mRNAs such as c-myc, c-fos, and granulocyte macrophage colony-stimulating factor. Direct binding studies demonstrated that Hel-N1 bound and formed multimers with c-myc 3' UTR mRNA and required, as a minimum, a specific 29-nucleotide stretch containing AUUUG, AUUUA, and GUUUUU. Deletion analysis demonstrated that a fragment of Hel-N1 containing 87 amino acids, encompassing the third RNA recognition motif, forms an RNA binding domain for the c-myc 3' UTR. In addition, Hel-N1 was shown to be reactive with autoantibodies from patients with paraneoplastic encephalomyelitis both before and after binding to c-myc mRNA.

• Authors: T D Levine, F Gao, P H King, L G Andrews, J D Keene
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 13 Issue 6 Pg. 3494-504 (Jun 1993) ISSN: 0270-7306 [Print] United States
• PMID: 8497264 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cytokines
• ELAV Proteins
• Proto-Oncogene Proteins
• RNA, Messenger
• RNA-Binding Proteins
• Recombinant Proteins
• Ribonucleoproteins
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Animals
• Base Sequence
• Cell Line
• Cloning, Molecular
• Cytokines (genetics)
• Drosophila melanogaster (genetics)
• ELAV Proteins
• Escherichia coli (genetics)
• Genes, fos
• Genes, myc
• Granulocyte-Macrophage Colony-Stimulating Factor (genetics)
• Humans
• Molecular Sequence Data
• Neurons (physiology)
• Oncogenes
• Plasmids
• Proto-Oncogene Proteins (genetics)
• RNA, Messenger (genetics, metabolism)
• RNA-Binding Proteins (genetics, metabolism)
• Recombinant Proteins (metabolism)
• Repetitive Sequences, Nucleic Acid
• Ribonucleoproteins (genetics)
• Sequence Homology, Nucleic Acid
• Transcription, Genetic
• Transfection