HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and sex-lethal

Szabó, Angela E.; Dalmau, Josep; Manley, Geoff; Rosenfeld, Myrna R.; Wong, Edmund; Henson, Joan M.; Posner, Jerome B.; Furneaux, Henry

doi:10.1016/0092-8674(91)90184-z

Cited by 540 publications

(414 citation statements)

References 20 publications

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“…ELAV proteins are a family of RNAbinding proteins essential in Drosophila for neural development (Campos et al, 1985). In mammals and in Xenopus, the Hu family consists of three members that are developmentally regulated and tissue-specific-Hel-N1 (also called HuB), HuC, and HuD-and one (HuR) that is ubiquitously expressed in all cell types (Szabo et al, 1991;King et al, 1994;Good, 1995;Ma et al, 1996;Antic and Keene, 1997). HuR is the best-characterized ELAV protein Brennan and Steitz, 2001;Wilusz et al, 2001).…”

Section: Hurmentioning

confidence: 99%

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Bevilacqua

Ceriani

Capaccioli

et al. 2003

Journal Cellular Physiology

293

259

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Recent evidence suggests that gene expression may be regulated, at least in part, at post-transcriptional level by factors inducing the extremely rapid degradation of messenger RNAs. These factors include reactions between adenyl-uridyl-rich elements (AREs) of the relevant mRNA and either specific proteins that bind to these elements or exosomes. This review deals with examples of the proteins (AU-rich binding proteins, AUBPs) and exosomes, which have been shown to form complexes with AREs and bring about rapid degradation of the relevant mRNA, and with certain other factors, which protect the RNA from such degradation. The biochemical and physiological factors underlying the stability of messenger RNAs carrying the ARE motifs will be reviewed in the light of their emerging significance for cell physiology, human pathology, and molecular medicine. We also consider the possible application of the results of recent insights into the mechanisms to pharmacological interventions to prevent or cure disorders, especially developmental disorders, which the suppression of gene expression may bring about. Molecular targeting of specific steps in protein degradation by synthetic compounds has already been utilized for the development of pharmacological therapies.

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Section: Hurmentioning

confidence: 99%

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Bevilacqua

Ceriani

Capaccioli

et al. 2003

Journal Cellular Physiology

293

259

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“…28,29 Hu proteins are RNA binding proteins highly homologous to the Drosophila protein ELAV (embryonic lethal abnormal vision) 30 and characterised by 2 tandem RNA recognition motifs (RRMs), an alternatively spliced basic domain and a third RRM. 26 The SEREX-defined antigens HuDpro1 and HuD1 are identical to HuDpro (M62843.1) and its splice variant HuD which lacks 14 amino acids of the basic protein domain. 26 The 5Ј untranslated region of HuDpro1 and HuD1 cDNAs extend beyond the published HuDpro/HuD 5Ј untranslated region and correspond to genomic sequences located on chromosome 1 (AL583843.3, bp 6939 -7204) right upstream of published HuD sequences (Fig.…”

Section: Serological Identification and Sequence Analysis Of Tumor-asmentioning

confidence: 99%

“…26 The SEREX-defined antigens HuDpro1 and HuD1 are identical to HuDpro (M62843.1) and its splice variant HuD which lacks 14 amino acids of the basic protein domain. 26 The 5Ј untranslated region of HuDpro1 and HuD1 cDNAs extend beyond the published HuDpro/HuD 5Ј untranslated region and correspond to genomic sequences located on chromosome 1 (AL583843.3, bp 6939 -7204) right upstream of published HuD sequences (Fig. 1a).…”

Section: Serological Identification and Sequence Analysis Of Tumor-asmentioning

confidence: 99%

Novel products of the HUD, HUC, NNP‐1 and α‐internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library

Behrends

Jandl

Golbeck

et al. 2002

Intl Journal of Cancer

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Autologous serological screening of a cDNA expression library (SEREX) derived from childhood neuroblastoma led to the identification of 10 different antigens, including 6 novel gene products. The novel antigen 018INX was derived from a small open reading frame in a region of ␣-internexin mRNA that was previously described as 3 untranslated region. 018INX thus represents a novel type of tumor antigen. Five novel gene products were derived from NNP-1 (NNP3) and Hu genes (HuC-L, HuD3, HuDY, HuD1pro c ). As indicated by sequence analysis, these antigens were generated by alternative splicing and/or alternative promoter usage or allelic polymorphism. mRNA expression analyses revealed different tissue restrictions of novel compared to known HuD and NNP-1 transcripts in normal and malignant tissues. The expressions patterns of distinct transcripts indicated potential clinical meanings as diagnostic and/or prognostic tissue markers. When kinetics of serum antibody titres against SEREX-defined antigens were compared to tumor load over time in our patient with neuroblastoma, we found 100-fold increases of anti-Hu and anti-018INX antibody titres preceding the clinical diagnosis of recurrent tumor growth after 2 years. When sera of pediatric patients with cancer (30) and healthy controls (30) were tested for humoral responses to SEREX-defined neuroblastoma antigens, we detected antibodies against all known antigens and NNP3 with low frequencies and titres in control sera, while anti-018INX and anti-Hu antibodies were found in cancer patients only. Our findings indicate that SEREX-defined tumor antigens might provide novel tools for understanding and treatment of this aggressive childhood malignancy.

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Section: Introductionmentioning

confidence: 99%

“…HuD, HuC, and Hel-N1 show 82 ± 90% sequence homology (King et al, 1994;Sakai et al, 1993;Szabo et al, 1991). In addition, they show an *54% homology to the Drosophila melanogaster RNA-binding proteins Sex-lethal and ELAV (King et al, 1994;Szabo et al, 1991), which participate in alternative splicing (Baker, 1989;Koushika et al, 1996). A role for the Hu proteins in neuronal di erentiation and survival is implied by their expression pattern in avian neural crest cells (Marusich and Weston, 1992;Marusich et al, 1994;Wakamatsu and Weston, 1997) and mouse embryos (Okano and Darnell, 1997), as well as in neurons of adult human central and peripheral nervous systems .…”

Section: Introductionmentioning

confidence: 99%

HuD, a neuronal-specific RNA-binding protein, is a putative regulator of N-myc pre-mRNA processing/stability in malignant human neuroblasts

et al. 1999

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N-myc gene copy numbers and transcription rates are similar in N (neuroblastic, tumorigenic) and S (nonneuronal, non-tumorigenic) neuroblastoma cells with chromosomally integrated ampli®ed N-myc genes. However, N cells show signi®cantly higher N-myc mRNA levels than S cells. Therefore, post-transcriptional control of N-myc gene expression must di er between these cell types. Since no di erences 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 di erences in N-myc expression arise primarily at the nuclear post-transcriptional level. The neuronal-speci®c RNA-binding Hu proteins are present in cytoplasmic and nuclear fractions of N cells and one of them, HuD, binds speci®cally 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 premRNA in N-type neuroblastoma cells.

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HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and sex-lethal

Cited by 540 publications

References 20 publications

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Novel products of the HUD, HUC, NNP‐1 and α‐internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library

HuD, a neuronal-specific RNA-binding protein, is a putative regulator of N-myc pre-mRNA processing/stability in malignant human neuroblasts

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