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Splicing dependency between EIF4G2 introns is mediated by exon definition and relies on a downstream splicing event

Item Type:Article
Title:Splicing dependency between EIF4G2 introns is mediated by exon definition and relies on a downstream splicing event
Creators: Pelletier, Marie-Lee, Vincent, Joëlle, Malo, Téa, Séguin, Camille, Tsybulskyi, Volodymyr ORCID logoORCID: https://orcid.org/0009-0002-4141-6291, Semenchenko, Egor ORCID logoORCID: https://orcid.org/0009-0007-5306-076X, Adamou, Ibrahim Soumana, Meyer, Irmtraud M. ORCID logoORCID: https://orcid.org/0000-0002-4048-3479 and Choquet, Karine
Abstract:In mammalian cells, pre-mRNA splicing requires the excision of multiple introns within the same nascent transcript through the coordinated action of the spliceosome and accessory factors. We and others recently demonstrated that multi-intron splicing follows a predetermined order, and that removal of proximal introns is coordinated. Notably, specific introns that are removed later within a transcript depend on their neighboring introns for efficient excision, but the underlying mechanisms remain unknown. Here, we investigated the determinants of splicing order and coordination using a multi-intron minigene splicing reporter based on the human gene EIF4G2. We found that dependency between a later-excised intron and its neighbor is partially mediated through the downstream 5′ splice site, consistent with the exon definition model, but is independent from intron length. Importantly, splicing coordination also relies on a prior downstream act of splicing, but not on specific cis regulatory elements in neighboring introns. Together, these findings improve our understanding of how distinct splicing reactions are connected and coordinated to produce mature RNA molecules.
Keywords:RNA Splicing, Splicing Coordination, Splicing Order, Exon Definition, Minigene
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:Elsevier / American Society for Biochemistry and Molecular Biology
Page Range:113304
Date:27 June 2026
Official Publication:https://doi.org/10.1016/j.jbc.2026.113304
PubMed:View item in PubMed
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