Recursive splicing in long vertebrate genes.

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Title: Recursive splicing in long vertebrate genes.
Author(s): Sibley, CR
Emmett, W
Blazquez, L
Faro, A
Haberman, N
Briese, M
Trabzuni, D
Ryten, M
Weale, ME
Hardy, J
Modic, M
Curk, T
Wilson, SW
Plagnol, V
Ule, J
Item Type: Journal Article
Abstract: It is generally believed that splicing removes introns as single units from precursor messenger RNA transcripts. However, some long Drosophila melanogaster introns contain a cryptic site, known as a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing. The extent to which recursive splicing occurs in other species and its mechanistic basis have not been examined. Here we identify highly conserved RS-sites in genes expressed in the mammalian brain that encode proteins functioning in neuronal development. Moreover, the RS-sites are found in some of the longest introns across vertebrates. We find that vertebrate recursive splicing requires initial definition of an RS-exon that follows the RS-site. The RS-exon is then excluded from the dominant mRNA isoform owing to competition with a reconstituted 5 splice site formed at the RS-site after the first splicing step. Conversely, the RS-exon is included when preceded by cryptic promoters or exons that fail to reconstitute an efficient 5 splice site. Most RS-exons contain a premature stop codon such that their inclusion can decrease mRNA stability. Thus, by establishing a binary splicing switch, RS-sites demarcate different mRNA isoforms emerging from long genes by coupling cryptic elements with inclusion of RS-exons.
Publication Date: 21-May-2015
Date of Acceptance: 9-Apr-2015
URI: http://hdl.handle.net/10044/1/30531
DOI: https://dx.doi.org/10.1038/nature14466
ISSN: 0028-0836
Publisher: Nature Publishing Group
Start Page: 371
End Page: 375
Journal / Book Title: Nature
Volume: 521
Issue: 7552
Copyright Statement: Copyright © 2015, Rights Managed by Nature Publishing Group
Keywords: Animals
Ankyrins
Base Sequence
Brain
Cell Adhesion Molecules
Codon, Terminator
Drosophila melanogaster
Exons
Female
Frontal Lobe
Humans
Immunoglobulins
Introns
Male
Promoter Regions, Genetic
RNA Isoforms
RNA Splice Sites
RNA Splicing
RNA Stability
Vertebrates
Zebrafish
Zebrafish Proteins
Brain
Frontal Lobe
Animals
Vertebrates
Zebrafish
Humans
Drosophila melanogaster
Ankyrins
Immunoglobulins
Zebrafish Proteins
Cell Adhesion Molecules
Codon, Terminator
RNA Splice Sites
RNA Splicing
Base Sequence
RNA Stability
Introns
Exons
Female
Male
Promoter Regions, Genetic
RNA Isoforms
Animals
Ankyrins
Base Sequence
Brain
Cell Adhesion Molecules
Codon, Terminator
Drosophila melanogaster
Exons
Female
Frontal Lobe
Humans
Immunoglobulins
Introns
Male
Promoter Regions, Genetic
RNA Isoforms
RNA Splice Sites
RNA Splicing
RNA Stability
Vertebrates
Zebrafish
Zebrafish Proteins
General Science & Technology
MD Multidisciplinary
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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