CDK11 is required for transcription of replication-dependent histone genes.
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
05
07
2019
accepted:
05
03
2020
pubmed:
6
5
2020
medline:
2
10
2020
entrez:
6
5
2020
Statut:
ppublish
Résumé
Replication-dependent histones (RDH) are required for packaging of newly synthetized DNA into nucleosomes during the S phase when their expression is highly upregulated. However, the mechanisms of this upregulation in metazoan cells remain poorly understood. Using iCLIP and ChIP-seq, we found that human cyclin-dependent kinase 11 (CDK11) associates with RNA and chromatin of RDH genes primarily in the S phase. Moreover, its amino-terminal region binds FLASH, an RDH-specific 3'-end processing factor, which keeps the kinase on the chromatin. CDK11 phosphorylates serine 2 (Ser2) of the carboxy-terminal domain of RNA polymerase II (RNAPII), which is initiated when RNAPII reaches the middle of RDH genes and is required for further RNAPII elongation and 3'-end processing. CDK11 depletion leads to decreased number of cells in S phase, likely owing to the function of CDK11 in RDH gene expression. Thus, the reliance of RDH expression on CDK11 could explain why CDK11 is essential for the growth of many cancers.
Identifiants
pubmed: 32367068
doi: 10.1038/s41594-020-0406-8
pii: 10.1038/s41594-020-0406-8
pmc: PMC7116321
mid: EMS85984
doi:
Substances chimiques
Apoptosis Regulatory Proteins
0
CASP8AP2 protein, human
0
Calcium-Binding Proteins
0
Chromatin
0
Histones
0
Serine
452VLY9402
RNA
63231-63-0
CDK19 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinases
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
500-510Subventions
Organisme : Medical Research Council
ID : FC001002
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001002
Pays : United Kingdom
Organisme : European Research Council
ID : 617837
Pays : International
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001002
Pays : United Kingdom
Références
Adelman, K. & Lis, J. T. Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans. Nat. Rev. Genet. 13, 720–731 (2012).
pubmed: 22986266
pmcid: 3552498
Fuda, N. J., Ardehali, M. B. & Lis, J. T. Defining mechanisms that regulate RNA polymerase II transcription in vivo. Nature 461, 186–192 (2009).
pubmed: 19741698
pmcid: 2833331
Proudfoot, N. J. Transcriptional termination in mammals: stopping the RNA polymerase II juggernaut. Science 352, aad9926 (2016).
pubmed: 27284201
pmcid: 5144996
Eick, D. & Geyer, M. The RNA polymerase II carboxy-terminal domain (CTD) code. Chem. Rev. 113, 8456–8490 (2013).
pubmed: 23952966
Harlen, K. M. & Churchman, L. S. The code and beyond: transcription regulation by the RNA polymerase II carboxy-terminal domain. Nat. Rev. Mol. Cell Biol. 18, 263–273 (2017).
pubmed: 28248323
Zaborowska, J., Egloff, S. & Murphy, S. The pol II CTD: new twists in the tail. Nat. Struct. Mol. Biol. 23, 771–777 (2016).
pubmed: 27605205
Jeronimo, C., Collin, P. & Robert, F. The RNA polymerase II CTD: the increasing complexity of a low-complexity protein domain. J. Mol. Biol. 428, 2607–2622 (2016).
pubmed: 26876604
Bentley, D. L. Coupling mRNA processing with transcription in time and space. Nat. Rev. Genet. 15, 163–175 (2014).
pubmed: 24514444
pmcid: 4304646
Hsin, J. P. & Manley, J. L. The RNA polymerase II CTD coordinates transcription and RNA processing. Genes Dev. 26, 2119–2137 (2012).
pubmed: 23028141
pmcid: 3465734
Herzel, L., Ottoz, D. S. M., Alpert, T. & Neugebauer, K. M. Splicing and transcription touch base: co-transcriptional spliceosome assembly and function. Nat. Rev. Mol. Cell Biol. 18, 637–650 (2017).
pubmed: 28792005
pmcid: 5928008
Marzluff, W. F. & Koreski, K. P. Birth and death of histone mRNAs. Trends Genet. 33, 745–759 (2017).
pubmed: 28867047
pmcid: 5645032
Duronio, R. J. & Marzluff, W. F. Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body. RNA Biol. 14, 726–738 (2017).
pubmed: 28059623
pmcid: 5519241
Sullivan, K. D., Steiniger, M. & Marzluff, W. F. A core complex of CPSF73, CPSF100, and Symplekin may form two different cleavage factors for processing of poly(A) and histone mRNAs. Mol. Cell 34, 322–332 (2009).
pubmed: 19450530
pmcid: 3503240
Kohn, M., Ihling, C., Sinz, A., Krohn, K. & Huttelmaier, S. The Y3** ncRNA promotes the 3′ end processing of histone mRNAs. Genes Dev. 29, 1998–2003 (2015).
pubmed: 26443846
pmcid: 4604341
Pirngruber, J. et al. CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3′-end processing. EMBO Rep. 10, 894–900 (2009).
pubmed: 19575011
pmcid: 2726677
Narita, T. et al. NELF interacts with CBC and participates in 3′ end processing of replication-dependent histone mRNAs. Mol. Cell 26, 349–365 (2007).
pubmed: 17499042
Saldi, T., Fong, N. & Bentley, D. L. Transcription elongation rate affects nascent histone pre-mRNA folding and 3′ end processing. Genes Dev. 32, 297–308 (2018).
pubmed: 29483154
pmcid: 5859970
Hsin, J. P., Sheth, A. & Manley, J. L. RNAP II CTD phosphorylated on threonine-4 is required for histone mRNA 3′ end processing. Science 334, 683–686 (2011).
pubmed: 22053051
pmcid: 3678764
Medlin, J. et al. P-TEFb is not an essential elongation factor for the intronless human U2 snRNA and histone H2b genes. EMBO J. 24, 4154–4165 (2005).
pubmed: 16308568
pmcid: 1356315
Hintermair, C. et al. Threonine-4 of mammalian RNA polymerase II CTD is targeted by Polo-like kinase 3 and required for transcriptional elongation. EMBO J. 31, 2784–2797 (2012).
pubmed: 22549466
pmcid: 3380212
Loyer, P. et al. Characterization of cyclin L1 and L2 interactions with CDK11 and splicing factors: influence of cyclin L isoforms on splice site selection. J. Biol. Chem. 283, 7721–7732 (2008).
pubmed: 18216018
Cornelis, S. et al. Identification and characterization of a novel cell cycle-regulated internal ribosome entry site. Mol. Cell 5, 597–605 (2000).
pubmed: 10882096
Hu, D., Valentine, M., Kidd, V. J. & Lahti, J. M. CDK11(p58) is required for the maintenance of sister chromatid cohesion. J. Cell Sci. 120, 2424–2434 (2007).
pubmed: 17606997
Petretti, C. et al. The PITSLRE/CDK11p58 protein kinase promotes centrosome maturation and bipolar spindle formation. EMBO Rep. 7, 418–424 (2006).
pubmed: 16462731
pmcid: 1456919
Zhou, Y., Shen, J. K., Hornicek, F. J., Kan, Q. & Duan, Z. The emerging roles and therapeutic potential of cyclin-dependent kinase 11 (CDK11) in human cancer. Oncotarget 7, 40846–40859 (2016).
pubmed: 27049727
pmcid: 5130049
Li, T., Inoue, A., Lahti, J. M. & Kidd, V. J. Failure to proliferate and mitotic arrest of CDK11(p110/p58)-null mutant mice at the blastocyst stage of embryonic cell development. Mol. Cell Biol. 24, 3188–3197 (2004).
pubmed: 15060143
pmcid: 381677
Hu, D., Mayeda, A., Trembley, J. H., Lahti, J. M. & Kidd, V. J. CDK11 complexes promote pre-mRNA splicing. J. Biol. Chem. 278, 8623–8629 (2003).
pubmed: 12501247
Trembley, J. H. et al. PITSLRE p110 protein kinases associate with transcription complexes and affect their activity. J. Biol. Chem. 277, 2589–2596 (2002).
pubmed: 11709559
Valente, S. T., Gilmartin, G. M., Venkatarama, K., Arriagada, G. & Goff, S. P. HIV-1 mRNA 3′ end processing is distinctively regulated by eIF3f, CDK11, and splice factor 9G8. Mol. Cell 36, 279–289 (2009).
pubmed: 19854136
pmcid: 3068534
Tiedemann, R. E. et al. Identification of molecular vulnerabilities in human multiple myeloma cells by RNA interference lethality screening of the druggable genome. Cancer Res. 72, 757–768 (2012).
pubmed: 22147262
Chi, Y. et al. Abnormal expression of CDK11p58 in prostate cancer. Cancer Cell Int. 14, 2 (2014).
pubmed: 24397471
pmcid: 3893504
Duan, Z. et al. Systematic kinome shRNA screening identifies CDK11 (PITSLRE) kinase expression is critical for osteosarcoma cell growth and proliferation. Clin. Cancer Res. 18, 4580–4588 (2012).
pubmed: 22791884
Kren, B. T. et al. Preclinical evaluation of cyclin dependent kinase 11 and casein kinase 2 survival kinases as RNA interference targets for triple negative breast cancer therapy. Breast Cancer Res. 17, 524 (2015).
Liu, X. et al. Cyclin-dependent kinase 11 (CDK11) is required for ovarian cancer cell growth in vitro and in vivo, and its inhibition causes apoptosis and sensitizes cells to paclitaxel. Mol. Cancer Ther. 15, 1691–1701 (2016).
pubmed: 27207777
pmcid: 4936930
Du, Y. et al. CDK11(p110) plays a critical role in the tumorigenicity of esophageal squamous cell carcinoma cells and is a potential drug target. Cell Cycle 18, 452–466 (2019).
pubmed: 30722725
pmcid: 6422471
Sokolova, M. et al. Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion. Cell Cycle 16, 189–199 (2017).
pubmed: 27929715
Yang, X. C., Burch, B. D., Yan, Y., Marzluff, W. F. & Dominski, Z. FLASH, a proapoptotic protein involved in activation of caspase-8, is essential for 3′ end processing of histone pre-mRNAs. Mol. Cell 36, 267–278 (2009).
pubmed: 19854135
pmcid: 2819824
Kohoutek, J. & Blazek, D. Cyclin K goes with Cdk12 and Cdk13. Cell Div. 7, 12 (2012).
pubmed: 22512864
pmcid: 3348076
Marzluff, W. F., Wagner, E. J. & Duronio, R. J. Metabolism and regulation of canonical histone mRNAs: life without a poly(A) tail. Nat. Rev. Genet. 9, 843–854 (2008).
pubmed: 18927579
pmcid: 2715827
Zhao, J. et al. NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. Genes Dev. 14, 2283–2297 (2000).
pubmed: 10995386
pmcid: 316937
Castello, A. et al. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 149, 1393–1406 (2012).
pubmed: 22658674
Baltz, A. G. et al. The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Mol. Cell 46, 674–690 (2012).
pubmed: 22681889
Konig, J. et al. iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat. Struct. Mol. Biol. 17, 909–915 (2010).
pubmed: 20601959
pmcid: 3000544
Van Nostrand, E. L. et al. Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP). Nat. Methods 13, 508–514 (2016).
pubmed: 27018577
pmcid: 4887338
Beltran, M. et al. The interaction of PRC2 with RNA or chromatin is mutually antagonistic. Genome Res. 26, 896–907 (2016).
pubmed: 27197219
pmcid: 4937559
Trembley, J. H., Hu, D., Slaughter, C. A., Lahti, J. M. & Kidd, V. J. Casein kinase 2 interacts with cyclin-dependent kinase 11 (CDK11) in vivo and phosphorylates both the RNA polymerase II carboxyl-terminal domain and CDK11 in vitro. J. Biol. Chem. 278, 2265–2270 (2003).
pubmed: 12429741
Pak, V. et al. CDK11 in TREX/THOC regulates HIV mRNA 3′ end processing. Cell Host Microbe 18, 560–570 (2015).
pubmed: 26567509
pmcid: 4648707
Peterlin, B. M. & Price, D. H. Controlling the elongation phase of transcription with P-TEFb. Mol. Cell 23, 297–305 (2006).
pubmed: 16885020
Bosken, C. A. et al. The structure and substrate specificity of human Cdk12/Cyclin K. Nat. Commun. 5, 3505 (2014).
pubmed: 24662513
pmcid: 3973122
Lyons, S. M. et al. A subset of replication-dependent histone mRNAs are expressed as polyadenylated RNAs in terminally differentiated tissues. Nucleic Acids Res. 44, 9190–9205 (2016).
pubmed: 27402160
pmcid: 5100578
Larochelle, S. et al. Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II. Nat. Struct. Mol. Biol. 19, 1108–1115 (2012).
pubmed: 23064645
pmcid: 3746743
Gruber, J. J. et al. Ars2 promotes proper replication-dependent histone mRNA 3′ end formation. Mol. Cell 45, 87–98 (2012).
pubmed: 22244333
pmcid: 3269315
Sullivan, K. D., Mullen, T. E., Marzluff, W. F. & Wagner, E. J. Knockdown of SLBP results in nuclear retention of histone mRNA. RNA 15, 459–472 (2009).
pubmed: 19155325
pmcid: 2657014
Drogat, J. et al. Cdk11-cyclinL controls the assembly of the RNA polymerase II mediator complex. Cell Rep. 2, 1068–1076 (2012).
pubmed: 23122962
Kim, D. U. et al. Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe. Nat. Biotechnol. 28, 617–623 (2010).
pubmed: 20473289
pmcid: 3962850
Kurat, C. F. et al. Regulation of histone gene transcription in yeast. Cell Mol. Life Sci. 71, 599–613 (2014).
pubmed: 23974242
Barcaroli, D. et al. FLASH is required for histone transcription and S-phase progression. Proc. Natl Acad. Sci. USA 103, 14808–14812 (2006).
pubmed: 17003125
Chapman, R. D. et al. Transcribing RNA polymerase II is phosphorylated at CTD residue serine-7. Science 318, 1780–1782 (2007).
pubmed: 18079404
Schuller, R. et al. Heptad-specific phosphorylation of RNA polymerase II CTD. Mol. Cell 61, 305–314 (2016).
pubmed: 26799765
Lin, A. et al. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci. Transl. Med. 11, eaaw8412 (2019).
pubmed: 31511426
Rouschop, K. M. et al. Deregulation of cap-dependent mRNA translation increases tumour radiosensitivity through reduction of the hypoxic fraction. Radiother. Oncol. 99, 385–391 (2011).
pubmed: 21665307
Huppertz, I. et al. iCLIP: protein-RNA interactions at nucleotide resolution. Methods 65, 274–287 (2014).
pubmed: 24184352
pmcid: 3988997
Roberts, T. C. et al. Quantification of nascent transcription by bromouridine immunocapture nuclear run-on RT-qPCR. Nat. Protoc. 10, 1198–1211 (2015).
pubmed: 26182239
pmcid: 4790731
Mahat, D. B. et al. Base-pair-resolution genome-wide mapping of active RNA polymerases using precision nuclear run-on (PRO-seq). Nat. Protoc. 11, 1455–1476 (2016).
pubmed: 27442863
pmcid: 5502525
Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2
Narita, T. et al. NELF interacts with CBC and participates in 3′ end processing of replication-dependent histone mRNAs. Mol. Cell 26, 349–365 (2007) .
pubmed: 17499042