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• W2313404803 abstract "Pre-mRNA molecules in humans contain mostly short internal exons flanked by longer introns. To explain the removal of such introns, exon recognition instead of intron recognition has been proposed. We studied this exon definition using designer exons (DEs) made up of three prototype modules of our own design: an exonic splicing enhancer (ESE), an exonic splicing silencer (ESS), and a Reference Sequence (R) predicted to be neither. Each DE was examined as the central exon in a three-exon minigene. DEs made of R modules showed a sharp size dependence, with exons shorter than 14 nt and longer than 174 nt splicing poorly. Changing the strengths of the splice sites improved longer exon splicing but worsened shorter exon splicing, effectively displacing the curve to the right. For the ESE we found, unexpectedly, that its enhancement efficiency was independent of its position within the exon. For the ESS we found a step-wise positional increase in its effects; it was most effective at the 3′ end of the exon. To apply these results quantitatively, we developed a biophysical model for exon definition of internal exons undergoing cotranscriptional splicing. This model features commitment to inclusion before the downstream exon is synthesized and competition between skipping and inclusion fates afterward. Collision of both exon ends to form an exon definition complex was incorporated to account for the effect of size; ESE/ESS effects were modeled on the basis of stabilization/destabilization. This model accurately predicted the outcome of independent experiments on more complex DEs that combined ESEs and ESSs." @default.
• W2313404803 created "2016-06-24" @default.
• W2313404803 creator A5050623276 @default.
• W2313404803 creator A5072321111 @default.
• W2313404803 creator A5081640435 @default.
• W2313404803 date "2014-12-09" @default.
• W2313404803 modified "2023-10-18" @default.
• W2313404803 title "Splicing of designer exons informs a biophysical model for exon definition" @default.
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• W2313404803 doi "https://doi.org/10.1261/rna.048009.114" @default.
• W2313404803 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4338349" @default.
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