Cited by 149Neuroblastoma Research and TreatmentsRNA Research and SplicingDevelopmental Biology and Gene Regulation

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Neuron-specific splicing of zinc finger transcription factor REST/NRSF/XBR is frequent in neuroblastomas and conserved in human, mouse and rat

Palm, Kaia, Metsis, Madis, Timmusk, Tõnis·1999·Molecular Brain Research

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Abstract

Neuron-restrictive silencer factor (NRSF), also known as repressor element RE1 binding transcription factor (REST) or repressor binding to the X2 box (XBR) (REST/NRSF/XBR), is a zinc finger transcription factor that during early embryogenesis is required to repress a subset of neuron-specific genes in non-neural tissues and undifferentiated neural precursors. We have previously shown that splicing within the coding region of rat REST/NRSF/XBR (rREST) generates several different transcripts all of which are expressed in the adult nervous system. rREST transcripts with short neuron-specific exons (exon N) have in-frame stop codons and encode truncated proteins which have an N-terminal repressor domain and weakened DNA binding activity. The aim of this study was to analyze the regulatory mechanisms underlying REST/NRSF/XBR activity in human and mouse as compared to rat. We show that the structure of REST/NRSF/XBR gene and its regulation by neuron-specific splicing is conserved in human, mouse and rat. Expression levels of REST/NRSF/XBR transcripts with the insertion of exon N are increased during the neuronal differentiation of mouse teratocarcinoma PCC7 and rat pheocromocytoma PC12 cells and are high in several human and mouse neuroblastoma cells as compared to the relatively low levels in the developing and adult nervous system. The exclusive expression of the neuronal forms of REST/NRSF/XBR mRNAs in mouse neuroblastoma Neuro-2A cells is not caused by rearrangement of the REST/NRSF/XBR gene nor by mutations in the sequence of the splice sites flanking exon N. These data suggest that changes in REST/NRSF/XBR splicing pattern may result from altered levels of splicing factors reflecting the formation and/or progression of neuroblastoma tumors.

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Self-citation
In PC12 Cells, Expression of Neurosecretion and Neurite Outgrowth are Governed by the Transcription Repressor REST/NRSF
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TAF4 Controls Differentiation of Human Neural Progenitor Cells Through hTAF4-TAFH Activity
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Self-citation

Authors: Palm, K., Metsis, M., & Timmusk, T.
Affiliations: Uppsala University (SE)
Tallinn University of Technology (EE)
Corresponding author: Timmusk, Tõnis
ORCID: Palm, Kaia
Metsis, Madis
Timmusk, Tõnis
Venue: Molecular Brain Research
Publisher: Elsevier BV
Published: 1999-09
Volume: 72
Issue: 1
Pages: 30-39
ISSN: 0169-328X (ISSN-L)
DOI: 10.1016/s0169-328x(99)00196-5
OpenAlex: W2031374484
Cited by: 144
References: 31
Citations by year: 2025: 3 · 2024: 13 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 7 · 2016: 5 · 2015: 5 · 2014: 11 · 2013: 9 · 2012: 11
FWCI: 3.01
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Molecular Brain Research (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Neuroblastoma Research and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords: neuroblastoma, zinc finger transcription factor, alternative splicing, neuronal differentiation, splicing factors, N2a cells, PC12 cells, truncated protein isoform
MeSH terms: RE1-Silencing Transcription Factor, Animals, Base Sequence, Chromosomes, Human, Pair 4, Exons, Glioma, Humans, Molecular Sequence Data, Neoplasm Proteins, Neuroblastoma, Neurons, Repressor Proteins, RNA Splicing, Sequence Homology, Nucleic Acid, Species Specificity, Transcription Factors, Tumor Cells, Cultured, Gene Expression Regulation, Neoplastic, Zinc Fingers, Consensus Sequence, Sequence Alignment, Teratocarcinoma, Protein Isoforms, Mice, Rats

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Neuron-specific splicing of zinc finger transcription factor REST/NRSF/XBR is frequent in neuroblastomas and conserved in human, mouse and rat

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