TET dioxygenases localize at splicing speckles and promote RNA splicing

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.

Identifier
Source https://tudatalib.ulb.tu-darmstadt.de/handle/tudatalib/4453
Metadata Access https://tudatalib.ulb.tu-darmstadt.de/oai/openairedata?verb=GetRecord&metadataPrefix=oai_datacite&identifier=oai:tudatalib.ulb.tu-darmstadt.de:tudatalib/4453
Provenance
Creator Hastert, Florian D.; Weber, Jasmin; Bauer, Christina; Zhadan, Andreas; Singh, Deepanshu N.D.; Dix, Thomas C.; Arnold, Roland; Bessonov, Sergey; Soller, Matthias; Leonhardt, Heinrich; Cardoso, M. Cristina; Arroyo, Maria
Publisher TU Darmstadt
Contributor TU Darmstadt
Publication Year 2024
Rights Creative Commons Attribution-NonCommercial 4.0; info:eu-repo/semantics/openAccess
OpenAccess true
Contact https://tudatalib.ulb.tu-darmstadt.de/page/contact
Representation
Language English
Resource Type Dataset
Format application/zip; application/octet-stream; application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
Version For review
Discipline Other