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Nat Struct Mol Biol. 2015 May;22(5):370-6. doi: 10.1038/nsmb.3005. Epub 2015 Apr 6.

A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature.

Author information

1
ATIP-AVENIR team, Institute of Human Genetics, CNRS UPR 1142, Montpellier, France.
2
Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
3
National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Abstract

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.

PMID:
25849144
PMCID:
PMC6322542
DOI:
10.1038/nsmb.3005
[Indexed for MEDLINE]
Free PMC Article

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