Paper Info
Title
Recursive splicing in long vertebrate genes.
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(1,2). 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 59 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 59 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.
Year
DOI
Venue
2015
10.1038/nature14466
NATURE
Keywords
DocType
Volume
Molecular neuroscience, RNA quality control, Sequence annotation, RNA splicing
Journal
521.0
Issue
ISSN
Citations 
7552.0
0028-0836
0
PageRank 
References 
Authors
0.34
2
16
Name
Order
Citations
PageRank
Christopher R. Sibley100.34
Lorea Blazquez200.34
Nejc Haberman300.34
Daniah Trabzuni400.34
Mina Ryten500.34
John Hardy640.71
Jernej Ule700.34
Michael Briese800.34
Miha Modic900.34
Warren Emmett1000.34
Vincent Plagnol11193.34
Ana Faro1200.34
Stephen W. Wilson1300.68
Mina Ryten1441.05
Michael E. Weale1540.71
Tomaž Curk16874.79