Expression, localization and tau exon 10 splicing activity of the brain RNA-binding protein TNRC4
| Autor: | Paul J. Chapple, Arvind Dev, Karen Anthony, Teresa Rodriguez Martin, Jean-Marc Gallo, Thomas A. Cooper |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Huntingtin
Blotting Western Tau protein Exonic splicing enhancer Fluorescent Antibody Technique Nerve Tissue Proteins tau Proteins RNA-binding protein CHO Cells Transfection Mice 03 medical and health sciences Exon Cricetulus 0302 clinical medicine Cricetinae Genetics Huntingtin Protein Animals CELF Proteins Humans Protein Isoforms Tissue Distribution RNA Messenger Molecular Biology Ataxin-1 Genetics (clinical) 030304 developmental biology Mice Knockout 0303 health sciences biology Reverse Transcriptase Polymerase Chain Reaction Alternative splicing Brain Nuclear Proteins RNA-Binding Proteins Exons General Medicine Molecular biology Peptide Fragments Alternative Splicing Ataxins RNA splicing biology.protein Rabbits Peptides 030217 neurology & neurosurgery |
| Zdroj: | Human Molecular Genetics. 16:2760-2769 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddm233 |
| Popis: | Elucidating the mechanisms of alternative splicing in the brain is a prerequisite to the understanding of the pathogenesis of major neurological diseases linked to impairment of pre-mRNA alternative splicing. The gene trinucleotide repeat-containing 4 (TNRC4) is predicted to encode a member of the CELF (CUG-BP- and ETR-3-like factors) family of RNA-binding proteins containing a 15-18-residue polyglutamine sequence. The TNRC4 transcript is selectively expressed in the brain. Using an anti-peptide antibody against the predicted sequence, we establish the presence of TNRC4 as a approximately 50 kDa protein in the brain. Full-length TNRC4 displays nuclear and cytoplasmic localizations in transfected cells, whereas a C-terminally truncated mutant is essentially confined to the cytoplasm. TNRC4 is not recruited into inclusions formed by polyglutamine-expanded ataxin-1 or huntingtin. TNRC4 activates tau exon 10 (E10) inclusion at high efficiency in transfected cells. TNRC4 contains two consecutive N-terminal RNA recognition motifs (RRMs) separated from the C-terminal RRM. Deletion and point mutant analysis show that the activity of TNRC4 on tau E10 splicing is mainly mediated by the RNA-binding activity of the second RRM and involves an intronic element of the tau pre-mRNA. The polyglutamine sequence has no effect on the activity of TNRC4 on tau E10 splicing. This study represents the first characterization of TNRC4 and provides further insight into the mechanisms of brain-specific alternative splicing and their possible pathological implications. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|