Informace o publikaci
The role of alkbh5 molecular interactions in mRNA processing, POSTER, Heidelberg, The epitranscriptome
| Autoři | |
|---|---|
| Rok publikování | 2025 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Přiložené soubory | |
| Popis | ALKBH5 is an m6A mRNA demethylase found across different species of life. At the cellular level, the removal of m6A by ALKBH5 is believed to affect the mRNA processing, export, localization, stability, and translation. ALKBH5 is essential for mouse germ line development and its altered expression has been linked to cancer progression in humans. However, ALKBH5 depletion has only minor effect on the overall m6A levels in nascent and steady state mRNAs. Despite multiple studies on ALKBH5, we are still lacking good understanding of its molecular function. Our recent interactome analyses revealed that ALKBH5 interacts with several mRNA processing and export factors. To further tackle the mechanism of ALKBH5 in these events, we performed transcriptomics analysis of ALKBH5 knock-out (KO) HEK293T cells. We observed dramatic expression changes in RNA pol-II transcripts accompanied by splicing alterations. To gain deeper insights into these splicing defects, we analysed publicly available datasets, where we observed exon skipping occurring more frequently than other splicing events. Furthermore, our results from high-throughput CRISPR/Cas9 genetic screening show potential genetic interactions between ALKBH5 and factors involved in splicing and mRNA export, corroborating our proteomic and transcriptomic data. Altogether, our results reveal the importance of ALKBH5 in mRNA processing and export. |