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• W1997530797 abstract "Accurate pre-mRNA splicing requires primary splicing signals, including the splice sites, a polypyrimidine tract, and a branch site, other splicing-regulatory elements (SREs). The SREs include exonic splicing enhancers (ESEs), exonic splicing silencers (ESSs), intronic splicing enhancers (ISEs), and intronic splicing silencers (ISSs), which are typically located near the splice sites. However, it is unclear to what extent splicing-driven selective pressure constrains exonic and intronic sequences, especially those distant from the splice sites. Here, we studied the distribution of SREs in human genes in terms of DNA strand-asymmetry patterns. Under a neutral evolution model, each mononucleotide or oligonucleotide should have a symmetric (Chargaff's second parity rule), or weakly asymmetric yet uniform, distribution throughout a pre-mRNA transcript. However, we found that large sets of unbiased, experimentally determined SREs show a distinct strand-asymmetry pattern that is inconsistent with the neutral evolution model, and reflects their functional roles in splicing. ESEs are selected in exons and depleted in introns and vice versa for ESSs. Surprisingly, this trend extends into deep intronic sequences, accounting for one third of the genome. Selection is detectable even at the mononucleotide level, so that the asymmetric base compositions of exons and introns are predictive of ESEs and ESSs. We developed a method that effectively predicts SREs based on strand asymmetry, expanding the current catalog of SREs. Our results suggest that human genes have been optimized for exon and intron discrimination through an RNA landscape shaped during evolution." @default.
• W1997530797 created "2016-06-24" @default.
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• W1997530797 creator A5049358254 @default.
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• W1997530797 date "2008-04-15" @default.
• W1997530797 modified "2023-10-16" @default.
• W1997530797 title "RNA landscape of evolution for optimal exon and intron discrimination" @default.
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• W1997530797 doi "https://doi.org/10.1073/pnas.0801692105" @default.
• W1997530797 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2311341" @default.
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