TET dioxygenases localize at splicing speckles and promote RNA splicing

dc.contributor.author Hastert, Florian D.
dc.contributor.author Weber, Jasmin
dc.contributor.author Bauer, Christina
dc.contributor.author Zhadan, Andreas
dc.contributor.author Singh, Deepanshu N.D.
dc.contributor.author Dix, Thomas C.
dc.contributor.author Arnold, Roland
dc.contributor.author Bessonov, Sergey
dc.contributor.author Soller, Matthias
dc.contributor.author Leonhardt, Heinrich
dc.contributor.author Cardoso, M. Cristina
dc.contributor.author Arroyo, Maria
dc.date.accessioned 2025-02-01T18:37:18Z
dc.date.available 2025-02-01T18:37:18Z
dc.date.created 2024-12
dc.date.issued 2025-02-01
dc.description The dynamic regulation of RNA metabolism plays a crucial role in cellular function, with emerging evidence suggesting a role for RNA modifications in this process. This study explores the relationship between RNA splicing and the TET dioxygenase activity, shedding light on the role of hm5C (RNA 5-hydroxymethylcytosine), and TET proteins, in RNA metabolism. Integrating data from mass spectrometry, AlphaFold structural modeling, microscopic analysis, and different functional assays including in vitro splicing, TET proteins were found to regulate splicing. We show that TET1, TET2, and TET3 interact with the splicing factors U2AF1 and U2AF2. Interestingly, TET dioxygenases localize in splicing speckles in mammalian and Drosophila cells. TET speckles association is RNA dependent, as it is TET interaction with splicing factors. Furthermore, in vitro splicing assays revealed that all three TET proteins promote splicing efficiency, and the oxidation of m5C to hm5C can restore splicing efficiency in vitro. The latter highlights the regulatory role of cytosine modifications in RNA metabolism. These findings provide insights into the complex interplay between RNA modifications and splicing, suggesting a multifaceted role for Tet proteins in RNA metabolism beyond its canonical DNA demethylation function. de_DE
dc.description.version For review de_DE
dc.identifier.uri https://tudatalib.ulb.tu-darmstadt.de/handle/tudatalib/4453
dc.identifier.uri https://doi.org/10.48328/tudatalib-1657
dc.language.iso en de_DE
dc.rights.licenseCC-BY-NC-4.0 (https://creativecommons.org/licenses/by-nc/4.0)
dc.subject RNA modifications de_DE
dc.subject splicing de_DE
dc.subject TET dioxygenases de_DE
dc.subject U2AF de_DE
dc.subject Epitranscriptomics de_DE
dc.subject 5-hydroymethylcytosine de_DE
dc.subject.classification 2.11-03
dc.subject.ddc 570
dc.title TET dioxygenases localize at splicing speckles and promote RNA splicing de_DE
dc.type Dataset de_DE
dc.type Text de_DE
dc.type Image de_DE
dc.type Model de_DE
dcterms.accessRights openAccess
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