Promoter Specificity and Transcription Levels Modulate Trans-Splicing Efficiency at the mod(mdg4) Locus in Drosophila

Beginyazova, Oguljan; Soldatova, Iuliia V.; Georgiev, Pavel; Tikhonov, Maxim

doi:10.3390/ijms262311609

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Promoter Specificity and Transcription Levels Modulate Trans-Splicing Efficiency at the mod(mdg4) Locus in Drosophila

Department of Regulation of Genetic Processes, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia

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Int. J. Mol. Sci. 2025, 26(23), 11609; https://doi.org/10.3390/ijms262311609

Submission received: 1 November 2025 / Revised: 22 November 2025 / Accepted: 28 November 2025 / Published: 29 November 2025

(This article belongs to the Section Molecular Biology)

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Abstract

Unlike canonical cis-splicing, trans-splicing combines exons from two distinct transcripts, creating chimeric mRNAs. One striking example is the mod(mdg4) locus in Drosophila, where all mRNAs, encompassing over 30 isoforms, are exclusively generated via trans-splicing, which integrates common constitutive exons with one of the alternative 3′ exons transcribed from independent promoters. This study analyzed the roles of the promoter, exons, and introns in trans-splicing, including in the constitutive part of the mod(mdg4) gene, using a previously validated model in the heterogeneous 22A genomic locus. We found that trans-splicing efficiency was significantly greater with the mod(mdg4) promoter compared to unrelated promoters with the similar transcription level. Trans-splicing efficiency correlates positively with transcriptional strength only at low transcription levels, and it does not change with further increases in mod(mdg4) transcription in the model system. The last common exon and the preceding intron of mod(mdg4) also play a minor role in enhancing trans-splicing. However, low levels of trans-splicing are maintained even when all sequences of the mod(mdg4) gene are replaced, except for the proximal part of the last intron, where trans-splicing is initiated.

Keywords: alternative splicing; trans-splicing; transcription factors; mod(mdg4); promoter; exon; intron

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MDPI and ACS Style

Beginyazova, O.; Soldatova, I.V.; Georgiev, P.; Tikhonov, M. Promoter Specificity and Transcription Levels Modulate Trans-Splicing Efficiency at the mod(mdg4) Locus in Drosophila. Int. J. Mol. Sci. 2025, 26, 11609. https://doi.org/10.3390/ijms262311609

AMA Style

Beginyazova O, Soldatova IV, Georgiev P, Tikhonov M. Promoter Specificity and Transcription Levels Modulate Trans-Splicing Efficiency at the mod(mdg4) Locus in Drosophila. International Journal of Molecular Sciences. 2025; 26(23):11609. https://doi.org/10.3390/ijms262311609

Chicago/Turabian Style

Beginyazova, Oguljan, Iuliia V. Soldatova, Pavel Georgiev, and Maxim Tikhonov. 2025. "Promoter Specificity and Transcription Levels Modulate Trans-Splicing Efficiency at the mod(mdg4) Locus in Drosophila" International Journal of Molecular Sciences 26, no. 23: 11609. https://doi.org/10.3390/ijms262311609

APA Style

Beginyazova, O., Soldatova, I. V., Georgiev, P., & Tikhonov, M. (2025). Promoter Specificity and Transcription Levels Modulate Trans-Splicing Efficiency at the mod(mdg4) Locus in Drosophila. International Journal of Molecular Sciences, 26(23), 11609. https://doi.org/10.3390/ijms262311609

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Promoter Specificity and Transcription Levels Modulate Trans-Splicing Efficiency at the mod(mdg4) Locus in Drosophila

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