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.
%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
}