ArticlePloS one2009
Evolution of alternative splicing regulation: changes in predicted exonic splicing regulators are not associated with changes in alternative splicing levels in primates.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Evolution of splicing regulatory networks in Drosophila.Genome research · 2014Article
- Genome-wide detection of condition-sensitive alternative splicing in Arabidopsis roots.Plant physiology · 2013Article
- Function of alternative splicing.Gene · 2013Review
- Origin and evolution of spliceosomal introns.Biology direct · 2012Review
- TIA1 prevents skipping of a critical exon associated with spinal muscular atrophy.Molecular and cellular biology · 2011Article
- Histone deacetylase activity modulates alternative splicing.PloS one · 2011Article
- Human brain evolution: harnessing the genomics (r)evolution to link genes, cognition, and behavior.Neuron · 2010Article
- The adaptive significance of unproductive alternative splicing in primates.RNA (New York, N.Y.) · 2010Article
- Functional properties and evolutionary splicing constraints on a composite exonic regulatory element of splicing in CFTR exon 12.Nucleic acids research · 2010Article
- Predicting functional alternative splicing by measuring RNA selection pressure from multigenome alignments.PLoS computational biology · 2009Article
- Divergence of exonic splicing elements after gene duplication and the impact on gene structures.Genome biology · 2009Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 3 countries.
Funding
Abstract
Alternative splicing is tightly regulated in a spatio-temporal and quantitative manner. This regulation is achieved by a complex interplay between spliceosomal (trans) factors that bind to different sequence (cis) elements. cis-elements reside in both introns and exons and may either enhance or silence splicing. Differential combinations of cis-elements allows for a huge diversity of overall splicing signals, together comprising a complex 'splicing code'. Many cis-elements have been identified, and their effects on exon inclusion levels demonstrated in reporter systems. However, the impact of interspecific differences in these elements on the evolution of alternative splicing levels has not yet been investigated at genomic level. Here we study the effect of interspecific differences in predicted exonic splicing regulators (ESRs) on exon inclusion levels in human and chimpanzee. For this purpose, we compiled and studied comprehensive datasets of predicted ESRs, identified by several computational and experimental approaches, as well as microarray data for changes in alternative splicing levels between human and chimpanzee. Surprisingly, we found no association between changes in predicted ESRs and changes in alternative splicing levels. This observation holds across different ESR exon positions, exon lengths, and 5' splice site strengths. We suggest that this lack of association is mainly due to the great importance of context for ESR functionality: many ESR-like motifs in primates may have little or no effect on splicing, and thus interspecific changes at short-time scales may primarily occur in these effectively neutral ESRs. These results underscore the difficulties of using current computational ESR prediction algorithms to identify truly functionally important motifs, and provide a cautionary tale for studies of the effect of SNPs on splicing in human disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.