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bioRxiv · 10.1101/2023.09.06.556538

Actin associates with actively elongating genes and binds directly to the Cdk9 subunit of P-TEFb

Kyheroinen, S.·Prajapati, B.·Sokolova, M.·Schmitz, M.·Geyer, M.·Vartiainen, M. K.
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Abstract

Nuclear actin has been demonstrated to be essential for optimal transcription, but the molecular mechanisms and direct binding partner for actin in the RNA polymerase complex have remained unknown. By using purified proteins in a variety of biochemical assays, we demonstrate a direct and specific interaction between monomeric actin and Cdk9, the kinase subunit of the positive transcription elongation factor b (P-TEFb) required for RNA polymerase II pause-release. This interaction efficiently prevents actin polymerization, is not dependent on kinase activity of Cdk9 and is not involved with releasing P-TEFb from its inhibitor 7SK snRNP complex. Supporting the specific role for actin in the elongation phase of transcription, chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) reveals that actin interacts with genes only upon their active transcription elongation. This study therefore provides novel insights into the mechanisms by which actin facilitates the transcription process.

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Kyheroinen, S., Prajapati, B., Sokolova, M., Schmitz, M., Geyer, M., Vartiainen, M. K.. 2023-09-07. Actin associates with actively elongating genes and binds directly to the Cdk9 subunit of P-TEFb. https://doi.org/10.1101/2023.09.06.556538

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