Abstract
BackgroundAlternative splicing has been proposed to increase transcript diversity and protein plasticity in eukaryotic organisms, but the extent to which this is the case is currently unclear, especially with regard to the diversification of molecular function. Eukaryotic splicing involves complex interactions of splicing factors and their targets. Inference of co-splicing networks capturing these types of interactions is important for understanding this crucial, highly regulated post-transcriptional process at the systems level.ResultsFirst, several transcript and protein attributes, including coding potential of transcripts and differences in functional domains of proteins, were compared between splice variants and protein isoforms to assess transcript and protein diversity in a biological system. Alternative splicing was shown to increase transcript and function-related protein diversity in developing Arabidopsis embryos. Second, CoSpliceNet, which integrates co-expression and motif discovery at splicing regulatory regions to infer co-splicing networks, was developed. CoSpliceNet was applied to temporal RNA sequencing data to identify candidate regulators of splicing events and predict RNA-binding motifs, some of which are supported by prior experimental evidence. Analysis of inferred splicing factor targets revealed an unexpected role for the unfolded protein response in embryo development.ConclusionsThe methods presented here can be used in any biological system to assess transcript diversity and protein plasticity and to predict candidate regulators, their targets, and RNA-binding motifs for splicing factors. CoSpliceNet is freely available at http://delasa.github.io/co-spliceNet/.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3172-6) contains supplementary material, which is available to authorized users.
Highlights
Alternative splicing has been proposed to increase transcript diversity and protein plasticity in eukaryotic organisms, but the extent to which this is the case is currently unclear, especially with regard to the diversification of molecular function
Alternative splicing (AS) and protein diversity in Arabidopsis embryo development In order to characterize the effect of AS on protein diversity, first, genes encoding pre-mRNAs that were alternatively spliced were identified
These genes encoded at least one non-canonical Splice variant (SV) (9834 transcripts in total, see Table 1 for definition of canonical SV) each, which was compared in each case with the canonical SV for protein diversity analysis
Summary
Alternative splicing has been proposed to increase transcript diversity and protein plasticity in eukaryotic organisms, but the extent to which this is the case is currently unclear, especially with regard to the diversification of molecular function. The position of splicing regulatory elements determines the action of the cognate SF because they affect the representation or misrepresentation of the splice site to the SF, which results in inclusion or exclusion of the corresponding RNA sequence in the final transcript [12]. This being the case, the production of spliced transcripts is dependent, in part, on the presence and activity of each SF required for the splicing of its corresponding pre-mRNAs. Coordination exists between the expression of an SF and the transcripts produced by that SF. Coordinated splicing (co-splicing) is defined here as the action of the spliceosome on a group of pre-mRNAs to produce a population of coordinately expressed and spliced transcripts
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