Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

Alternative splicing is a key step in eukaryotic gene expression that allows for the production of multiple transcript and protein isoforms from the same gene. Even though splicing is perturbed in many diseases, we currently lack insights into regulatory mechanisms promoting its precision and efficiency. We analyze high-throughput mutagenesis data obtained for an alternatively spliced exon in the proto-oncogene RON and determine the functional units that control this splicing event. Using mathematical modeling of distinct splicing mechanisms, we show that alternative splicing is based in RON on a so-called "exon definition" mechanism. Here, the recognition of the adjacent exons by the spliceosome is required for removal of an intron. We use our model to analyze the differences between the exon and intron definition scenarios and find that exon definition prevents the accumulation of deleterious, partially spliced retention products during alternative splicing regulation. Furthermore, it modularizes splicing control, as multiple regulatory inputs are integrated into a common net input, irrespective of the location and nature of the corresponding cis-regulatory elements in the pre-messenger RNA. Our analysis suggests that exon definition promotes robust and reliable splicing outcomes in RON splicing. Copyright © 2020 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Citation

Mihaela Enculescu, Simon Braun, Samarth Thonta Setty, Anke Busch, Kathi Zarnack, Julian König, Stefan Legewie. Exon Definition Facilitates Reliable Control of Alternative Splicing in the RON Proto-Oncogene. Biophysical journal. 2020 Apr 21;118(8):2027-2041

Expand section icon Mesh Tags


PMID: 32336349

View Full Text