%0 Journal Article %1 ji_hnrnp_2022 %A Ji, Changhe %A Deng, Chunchu %A Antor, Katharina %A Bischler, Thorsten %A Schneider, Cornelius %A Fischer, Utz %A Sendtner, Michael %A Briese, Michael %D 2022 %J EMBO reports %K 7SK BRD4 P-TEFb hnRNP_R myown transcription %P e55432 %R 10.15252/embr.202255432 %T hnRNP R negatively regulates transcription by modulating the association of P-TEFb with 7SK and BRD4 %X The P-TEFb complex promotes transcription elongation by releasing paused RNA polymerase II. P-TEFb itself is known to be inactivated through binding to the non-coding RNA 7SK but there is only limited information about mechanisms regulating their association. Here, we show that cells deficient in the RNA-binding protein hnRNP R, a known 7SK interactor, exhibit increased transcription due to phosphorylation of RNA polymerase II. Intriguingly, loss of hnRNP R promotes the release of P-TEFb from 7SK, accompanied by enhanced hnRNP A1 binding to 7SK. Additionally, we found that hnRNP R interacts with BRD4, and that hnRNP R depletion increases BRD4 binding to the P-TEFb component CDK9. Finally, CDK9 is stabilized upon loss of hnRNP R and its association with Cyclin K is enhanced. Together, our results indicate that hnRNP R negatively regulates transcription by modulating the activity and stability of the P-TEFb complex, exemplifying the multimodal regulation of P-TEFb by an RNA-binding protein.

@article{ji_hnrnp_2022, abstract = {The P-TEFb complex promotes transcription elongation by releasing paused RNA polymerase II. P-TEFb itself is known to be inactivated through binding to the non-coding RNA 7SK but there is only limited information about mechanisms regulating their association. Here, we show that cells deficient in the RNA-binding protein hnRNP R, a known 7SK interactor, exhibit increased transcription due to phosphorylation of RNA polymerase II. Intriguingly, loss of hnRNP R promotes the release of P-TEFb from 7SK, accompanied by enhanced hnRNP A1 binding to 7SK. Additionally, we found that hnRNP R interacts with BRD4, and that hnRNP R depletion increases BRD4 binding to the P-TEFb component CDK9. Finally, CDK9 is stabilized upon loss of hnRNP R and its association with Cyclin K is enhanced. Together, our results indicate that hnRNP R negatively regulates transcription by modulating the activity and stability of the P-TEFb complex, exemplifying the multimodal regulation of P-TEFb by an RNA-binding protein.}, added-at = {2022-07-21T10:55:00.000+0200}, author = {Ji, Changhe and Deng, Chunchu and Antor, Katharina and Bischler, Thorsten and Schneider, Cornelius and Fischer, Utz and Sendtner, Michael and Briese, Michael}, biburl = {https://www.bibsonomy.org/bibtex/2eeb36ae448417aa063dce8a73af591b8/cusysmed}, day = 20, doi = {10.15252/embr.202255432}, interhash = {acd6f578675a46bbd2df5119bf4130c6}, intrahash = {eeb36ae448417aa063dce8a73af591b8}, issn = {1469-3178}, journal = {EMBO reports}, keywords = {7SK BRD4 P-TEFb hnRNP_R myown transcription}, language = {eng}, month = jul, pages = {e55432}, pmid = {35856391}, timestamp = {2022-10-07T14:48:05.000+0200}, title = {hnRNP R negatively regulates transcription by modulating the association of P-TEFb with 7SK and BRD4}, year = 2022 }