Co-transcriptional splicing is delayed in the highly expressed thyroglobulin gene
Journal of Cell Science article from the Solovei lab, with first author IRTG member Simon Ullrich
11.02.2025
Simon Ullrich, Iliya Nadelson, Stefan Krebs, Helmut Blum, Heinrich Leonhardt and Irina Solovei (2025 Feb 11) Co-transcriptional splicing is delayed in the highly expressed thyroglobulin gene. Journal of Cell Science 138, jcs263872. doi:10.1242/jcs.263872
Abstract cited directly from the article:
Transcription of the majority of eukaryotic genes is accompanied by splicing. The timing of splicing varies significantly between introns,
transcripts, genes and species. Although quick co-transcriptional intron removal has been demonstrated for many mammalian genes,
most splicing events do not occur immediately after intron synthesis. In this study, we utilized the highly expressed Tg gene, which forms exceptionally long transcription loops, providing a convenient model for studying splicing dynamics using advanced light microscopy. Using single-cell oligopainting, we observed a splicing delay occurring several tens of kilobases downstream of a transcribed
intron, a finding supported by standard cell population analyses. We speculate that this phenomenon is due to the abnormally high
transcriptional rate of the Tg gene, which might lead to a localized deficiency in splicing factors and, consequently, delayed
spliceosome assembly on thousands of nascent transcripts decorating the gene. Additionally, we found that, in contrast to what
is seen for short introns (<10 kb), the long Tg intron (>50 kb) is spliced promptly, providing further support for the idea that intron length might modulate splicing speed.