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Qi, Q.* ; Tomaz da Silva, P.* ; Vangalis, V.* ; Dockx, S.* ; Steensels, J.* ; Voordeckers, K.* ; Gagneur, J. ; Verstrepen, K.J.*

Intron location and sequence modulate gene expression in Yarrowia lipolytica.

Nucleic Acids Res. 54:gkag650 (2026)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
Introns are widespread among eukaryotic genomes. While intron-containing genes often show higher expression than genes lacking introns, the intron features influencing gene expression remain largely elusive. Here, we systematically characterize the intron landscape of Yarrowia lipolytica, an oleaginous yeast that is increasingly used as a microbial cell factory. Transcriptome analysis across 12 environments identified 2421 introns in 1430 genes, including 1302 newly discovered introns and 479 newly annotated intron-containing genes. We find that intron-containing genes exhibit higher and more stable expression across conditions and identify six key intron features, including the 5′ splice motif, 3′ splice motif, branch point motif, distance from branch point to 3′ splice site, GC content, and intron size, that influence splicing efficiency and gene expression. A linear regression model based on these features robustly captures the intron’s effect on gene expression, enabling us to select and test 55 different introns that modulate expression of a reporter gene by 200-fold. Moreover, we demonstrate that intron effects are robust across genomic contexts and identify a previously uncharacterized intron, I3, that strongly enhances gene expression and protein production. Together, our results provide new fundamental insights and open new avenues for using introns as regulatory elements.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Mediated Enhancement; Splicing Efficiency; Protein Expression; Rna; Evolution; Reveals; Transcription; Definition; Mechanisms; Genomes
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Journal Nucleic Acids Research
Quellenangaben Volume: 54, Issue: 12, Pages: , Article Number: gkag650 Supplement: ,
Publisher Oxford University Press
Publishing Place Great Clarendon St, Oxford Ox2 6dp, England
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants FWO
VLAIO Innovation Mandate
ESI Moonshot project
VIB Grand Challenges project
ERC Synergy
IT Infrastructure for Computational Molecular Medicine
FWO International Research Infrastructure
Deutsche Forschungsgemeinschaft