Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues
Top Cited Papers
- 21 December 2012
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 338 (6114), 1593-1599
- https://doi.org/10.1126/science.1228186
Abstract
Most mammalian genes produce multiple distinct messenger RNAs through alternative splicing, but the extent of splicing conservation is not clear. To assess tissue-specific transcriptome variation across mammals, we sequenced complementary DNA from nine tissues from four mammals and one bird in biological triplicate, at unprecedented depth. We find that while tissue-specific gene expression programs are largely conserved, alternative splicing is well conserved in only a subset of tissues and is frequently lineage-specific. Thousands of previously unknown, lineage-specific, and conserved alternative exons were identified; widely conserved alternative exons had signatures of binding by MBNL, PTB, RBFOX, STAR, and TIA family splicing factors, implicating them as ancestral mammalian splicing regulators. Our data also indicate that alternative splicing often alters protein phosphorylatability, delimiting the scope of kinase signaling.Keywords
This publication has 45 references indexed in Scilit:
- Tissue-Specific Splicing of Disordered Segments that Embed Binding Motifs Rewires Protein Interaction NetworksMolecular Cell, 2012
- Integrative Genome-wide Analysis Reveals Cooperative Regulation of Alternative Splicing by hnRNP ProteinsCell Reports, 2012
- The evolution of gene expression levels in mammalian organsNature, 2011
- A high-resolution map of human evolutionary constraint using 29 mammalsNature, 2011
- A Tissue-Specific Atlas of Mouse Protein Phosphorylation and ExpressionCell, 2010
- Analysis and design of RNA sequencing experiments for identifying isoform regulationNature Methods, 2010
- Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiationNature Biotechnology, 2010
- An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cellsNature Structural & Molecular Biology, 2009
- Alternative isoform regulation in human tissue transcriptomesNature, 2008
- PhosphoSite: A bioinformatics resource dedicated to physiological protein phosphorylationProteomics, 2004