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Title:
A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature | Nature Structural & Molecular Biology
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The evolutionarily conserved antisense long noncoding RNA asFGFR2 influences cell type–specific alternative-splicing patterns of FGFR2 by recruiting chromatin modifiers to the locus. Alternative pre-mRNA splicing is a highly cell type–specific process essential to generating protein diversity. However, the mechanisms responsible for the establishment and maintenance of heritable cell-specific alternative-splicing programs are poorly understood. Recent observations point to a role of histone modifications in the regulation of alternative splicing. Here we report a new mechanism of chromatin-mediated splicing control involving a long noncoding RNA (lncRNA). We have identified an evolutionarily conserved nuclear antisense lncRNA, generated from within the human FGFR2 locus, that promotes epithelial-specific alternative splicing of FGFR2. The lncRNA acts through recruitment of Polycomb-group proteins and the histone demethylase KDM2a to create a chromatin environment that impairs binding of a repressive chromatin-splicing adaptor complex important for mesenchymal-specific splicing. Our results uncover a new function for lncRNAs in the establishment and maintenance of cell-specific alternative splicing via modulation of chromatin signatures.
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headline:A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature
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Alternative splicing
Histone post-translational modifications
Long non-coding RNAs
Life Sciences
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Protein Structure
Membrane Biology
Biological Microscopy
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description:The evolutionarily conserved antisense long noncoding RNA asFGFR2 influences cell typeâspecific alternative-splicing patterns of FGFR2 by recruiting chromatin modifiers to the locus. Alternative pre-mRNA splicing is a highly cell typeâspecific process essential to generating protein diversity. However, the mechanisms responsible for the establishment and maintenance of heritable cell-specific alternative-splicing programs are poorly understood. Recent observations point to a role of histone modifications in the regulation of alternative splicing. Here we report a new mechanism of chromatin-mediated splicing control involving a long noncoding RNA (lncRNA). We have identified an evolutionarily conserved nuclear antisense lncRNA, generated from within the human FGFR2 locus, that promotes epithelial-specific alternative splicing of FGFR2. The lncRNA acts through recruitment of Polycomb-group proteins and the histone demethylase KDM2a to create a chromatin environment that impairs binding of a repressive chromatin-splicing adaptor complex important for mesenchymal-specific splicing. Our results uncover a new function for lncRNAs in the establishment and maintenance of cell-specific alternative splicing via modulation of chromatin signatures.
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Histone post-translational modifications
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Protein Structure
Membrane Biology
Biological Microscopy
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