The role of Mediator and Little Elongation Complex in transcription termination.

Cell Line, Tumor Gene Expression Regulation / genetics HCT116 Cells HEK293 Cells HeLa Cells Humans Mediator Complex / genetics Nuclear Proteins / metabolism RNA Cap-Binding Proteins / metabolism RNA Polymerase II / metabolism RNA, Small Nuclear / genetics Transcription Factors / metabolism Transcription Termination, Genetic / physiology Transcriptional Elongation Factors / genetics

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
26 02 2020

Historique:

received: 02 02 2019

accepted: 08 02 2020

entrez: 28 2 2020

pubmed: 28 2 2020

medline: 1 5 2020

Statut: epublish

Résumé

Mediator is a coregulatory complex that regulates transcription of Pol II-dependent genes. Previously, we showed that human Mediator subunit MED26 plays a role in the recruitment of Super Elongation Complex (SEC) or Little Elongation Complex (LEC) to regulate the expression of certain genes. MED26 plays a role in recruiting SEC to protein-coding genes including c-myc and LEC to small nuclear RNA (snRNA) genes. However, how MED26 engages SEC or LEC to regulate distinct genes is unclear. Here, we provide evidence that MED26 recruits LEC to modulate transcription termination of non-polyadenylated transcripts including snRNAs and mRNAs encoding replication-dependent histone (RDH) at Cajal bodies. Our findings indicate that LEC recruited by MED26 promotes efficient transcription termination by Pol II through interaction with CBC-ARS2 and NELF/DSIF, and promotes 3' end processing by enhancing recruitment of Integrator or Heat Labile Factor to snRNA or RDH genes, respectively.

Identifiants

DOI: 10.1038/s41467-020-14849-1 PMID: 32102997 PMC: PMC7044329

pubmed: 32102997

doi: 10.1038/s41467-020-14849-1

pii: 10.1038/s41467-020-14849-1

pmc: PMC7044329

doi:

Substances chimiques

MED26 protein, human 0

Mediator Complex 0

NSMF protein, human 0

Nuclear Proteins 0

RNA Cap-Binding Proteins 0

RNA, Small Nuclear 0

SRRT protein, human 0

SUPT5H protein, human 0

Transcription Factors 0

Transcriptional Elongation Factors 0

RNA Polymerase II EC 2.7.7.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1063

Références

Levine, M., Cattoglio, C. & Tjian, R. Looping back to leap forward: transcription enters a new era. Cell 157, 13–25 (2014).

pubmed: 24679523 pmcid: 4059561 doi: 10.1016/j.cell.2014.02.009

Richard, P. & Manley, J. L. Transcription termination by nuclear RNA polymerases. Genes Dev. 23, 1247–1269 (2009).

Guiro, J. & Murphy, S. Regulation of expression of human RNA polymerase II-transcribed snRNA genes. Open Biol 7, https://doi.org/10.1098/rsob.170073 (2017).

pubmed: 28615474 pmcid: 5493778 doi: 10.1098/rsob.170073

Gilmartin, G. M. Eukaryotic mRNA 3′ processing: a common means to different ends. Genes Dev. 19, 2517–2521 (2005).

pubmed: 16264187 doi: 10.1101/gad.1378105 pmcid: 16264187

Chen, J. & Wagner, E. J. snRNA 3′ end formation: the dawn of the Integrator complex. Biochem. Soc. Trans. 38, 1082–1087 (2010).

pubmed: 20659008 pmcid: 3969742 doi: 10.1042/BST0381082

Romeo, V. & Schumperli, D. Cycling in the nucleus: regulation of RNA 3′ processing and nuclear organization of replication-dependent histone genes. Curr. Opin. Cell Biol. 40, 23–31 (2016).

pubmed: 26895140 doi: 10.1016/j.ceb.2016.01.015 pmcid: 26895140

Dominski, Z. & Marzluff, W. F. Formation of the 3′ end of histone mRNA: getting closer to the end. Gene 396, 373–390 (2007).

pubmed: 17531405 pmcid: 2888136 doi: 10.1016/j.gene.2007.04.021

Yang, X. C. et al. A complex containing the CPSF73 endonuclease and other polyadenylation factors associates with U7 snRNP and is recruited to histone pre-mRNA for 3′-end processing. Mol. Cell. Biol. 33, 28–37 (2013).

pubmed: 23071092 pmcid: 3536302 doi: 10.1128/MCB.00653-12

Skrajna, A., Yang, X. C., Dadlez, M., Marzluff, W. F. & Dominski, Z. Protein composition of catalytically active U7-dependent processing complexes assembled on histone pre-mRNA containing biotin and a photo-cleavable linker. Nucleic Acids Res. 46, 4752–4770 (2018).

pubmed: 29529248 pmcid: 5961079 doi: 10.1093/nar/gky133

Dominski, Z., Yang, X. C. & Marzluff, W. F. The polyadenylation factor CPSF-73 is involved in histone-pre-mRNA processing. Cell 123, 37–48 (2005).

pubmed: 16213211 doi: 10.1016/j.cell.2005.08.002 pmcid: 16213211

Romeo, V., Griesbach, E. & Schumperli, D. CstF64: cell cycle regulation and functional role in 3′ end processing of replication-dependent histone mRNAs. Mol. Cell. Biol. 34, 4272–4284 (2014).

pubmed: 25266659 pmcid: 4248742 doi: 10.1128/MCB.00791-14

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 doi: 10.1093/nar/gkw418

Baillat, D. et al. Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II. Cell 123, 265–276 (2005).

pubmed: 16239144 doi: 10.1016/j.cell.2005.08.019 pmcid: 16239144

Yamamoto, J. et al. DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes. Nat. Commun. 5, 4263 (2014).

pubmed: 24968874 doi: 10.1038/ncomms5263 pmcid: 24968874

Andersen, P. R. et al. The human cap-binding complex is functionally connected to the nuclear RNA exosome. Nat. Struct. Mol. Biol. 20, 1367–1376 (2013).

pubmed: 24270879 pmcid: 3923317 doi: 10.1038/nsmb.2703

Hallais, M. et al. CBC-ARS2 stimulates 3′-end maturation of multiple RNA families and favors cap-proximal processing. Nat. Struct. Mol. Biol. 20, 1358–1366 (2013).

pubmed: 24270878 doi: 10.1038/nsmb.2720 pmcid: 24270878

Wada, T. et al. DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. Genes Dev. 12, 343–356 (1998).

pubmed: 9450929 pmcid: 316480 doi: 10.1101/gad.12.3.343

Yamaguchi, Y. et al. NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Cell 97, 41–51 (1999).

pubmed: 10199401 doi: 10.1016/S0092-8674(00)80713-8 pmcid: 10199401

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 doi: 10.1016/j.molcel.2007.04.011 pmcid: 17499042

Conaway, R. C. & Conaway, J. W. The Mediator complex and transcription elongation. Biochim. Biophys. Acta 1829, 69–75 (2013).

pubmed: 22983086 doi: 10.1016/j.bbagrm.2012.08.017 pmcid: 22983086

Malik, S. Eukaryotic transcription regulation: getting to the heart of the matter: commentary on mediator architecture and RNA polymerase II function by Plaschka et al. J. Mol. Biol. 428, 2575–2580 (2016).

pubmed: 27056597 doi: 10.1016/j.jmb.2016.04.001 pmcid: 27056597

Allen, B. L. & Taatjes, D. J. The Mediator complex: a central integrator of transcription. Nat. Rev. Mol. Cell. Biol. 16, 155–166 (2015).

pubmed: 25693131 pmcid: 4963239 doi: 10.1038/nrm3951

Takahashi, H. et al. Human mediator subunit MED26 functions as a docking site for transcription elongation factors. Cell 146, 92–104 (2011).

pubmed: 21729782 pmcid: 3145325 doi: 10.1016/j.cell.2011.06.005

Takahashi, H. et al. MED26 regulates the transcription of snRNA genes through the recruitment of little elongation complex. Nat. Commun. 6, 5941 (2015).

pubmed: 25575120 pmcid: 4646223 doi: 10.1038/ncomms6941

Shilatifard, A., Lane, W. S., Jackson, K. W., Conaway, R. C. & Conaway, J. W. An RNA polymerase II elongation factor encoded by the human ELL gene. Science 271, 1873–1876 (1996).

pubmed: 8596958 doi: 10.1126/science.271.5257.1873 pmcid: 8596958

Kong, S. E., Banks, C. A., Shilatifard, A., Conaway, J. W. & Conaway, R. C. ELL-associated factors 1 and 2 are positive regulators of RNA polymerase II elongation factor ELL. Proc. Natl Acad. Sci. USA 102, 10094–10098 (2005).

pubmed: 16006523 doi: 10.1073/pnas.0503017102 pmcid: 16006523

Luo, Z., Lin, C. & Shilatifard, A. The super elongation complex (SEC) family in transcriptional control. Nat. Rev. Mol. Cell. Biol. 13, 543–547 (2012).

pubmed: 22895430 doi: 10.1038/nrm3417 pmcid: 22895430

He, N. et al. HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. Mol. Cell 38, 428–438 (2010).

pubmed: 20471948 pmcid: 3085314 doi: 10.1016/j.molcel.2010.04.013

Lin, C. et al. AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. Mol. Cell 37, 429–437 (2010).

pubmed: 20159561 pmcid: 2872029 doi: 10.1016/j.molcel.2010.01.026

Sobhian, B. et al. HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP. Mol. Cell 38, 439–451 (2010).

pubmed: 20471949 pmcid: 3595998 doi: 10.1016/j.molcel.2010.04.012

Hu, D. et al. The little elongation complex functions at initiation and elongation phases of snRNA gene transcription. Mol. Cell 51, 493–505 (2013).

pubmed: 23932780 pmcid: 4104523 doi: 10.1016/j.molcel.2013.07.003

Smith, E. R. et al. The little elongation complex regulates small nuclear RNA transcription. Mol. Cell 44, 954–965 (2011).

pubmed: 22195968 pmcid: 3249835 doi: 10.1016/j.molcel.2011.12.008

Hutten, S., Chachami, G., Winter, U., Melchior, F. & Lamond, A. I. A role for the Cajal-body-associated SUMO isopeptidase USPL1 in snRNA transcription mediated by RNA polymerase II. J. Cell Sci. 127, 1065–1078 (2014).

pubmed: 24413172 pmcid: 3937775 doi: 10.1242/jcs.141788

Takata, H., Nishijima, H., Maeshima, K. & Shibahara, K. The integrator complex is required for integrity of Cajal bodies. J. Cell Sci. 125, 166–175 (2012).

pubmed: 22250197 doi: 10.1242/jcs.090837 pmcid: 22250197

Baird, T. D. et al. ICE1 promotes the link between splicing and nonsense-mediated mRNA decay. eLife 7, https://doi.org/10.7554/eLife.33178 (2018).

Kiss, T. Biogenesis of small nuclear RNPs. J. Cell Sci. 117, 5949–5951 (2004).

pubmed: 15564372 doi: 10.1242/jcs.01487

Bongiorno-Borbone, L. et al. FLASH and NPAT positive but not Coilin positive Cajal Bodies correlate with cell ploidy. Cell Cycle 7, 2357–2367 (2008).

pubmed: 18677100 doi: 10.4161/cc.6344 pmcid: 18677100

Wang, Q. et al. Cajal bodies are linked to genome conformation. Nat. Commun. 7, 10966 (2016).

pubmed: 26997247 pmcid: 4802181 doi: 10.1038/ncomms10966

Okada, Y. & Nakagawa, S. in Nuclear Bodies and Noncoding RNAs: Methods and Protocols (eds Nakagawa, S. & Hirose, T.) (Springer, New York, 2015).

Ezzeddine, N. et al. A subset of Drosophila integrator proteins is essential for efficient U7 snRNA and spliceosomal snRNA 3′-end formation. Mol. Cell. Biol. 31, 328–341 (2011).

pubmed: 21078872 doi: 10.1128/MCB.00943-10 pmcid: 21078872

de Vegvar, H. E., Lund, E. & Dahlberg, J. E. 3′ End formation of U1 snRNA precursors is coupled to transcription from snRNA promoters. Cell 47, 259–266 (1986).

pubmed: 3021336 doi: 10.1016/0092-8674(86)90448-4 pmcid: 3021336

Hernandez, N. & Weiner, A. M. Formation of the 3′ end of U1 snRNA requires compatible snRNA promoter elements. Cell 47, 249–258 (1986).

pubmed: 3768956 doi: 10.1016/0092-8674(86)90447-2 pmcid: 3768956

Brocato, J. et al. Arsenic induces polyadenylation of canonical histone mRNA by down-regulating stem-loop-binding protein gene expression. J. Biol. Chem. 289, 31751–31764 (2014).

pubmed: 25266719 pmcid: 4231654 doi: 10.1074/jbc.M114.591883

Brocato, J. et al. A potential new mechanism of arsenic carcinogenesis: depletion of stem-loop binding protein and increase in polyadenylated canonical histone H3.1 mRNA. Biol. Trace Elem. Res. 166, 72–81 (2015).

pubmed: 25893362 pmcid: 4470754 doi: 10.1007/s12011-015-0296-5

Costa, M. Review of arsenic toxicity, speciation and polyadenylation of canonical histones. Toxicol. Appl Pharm. 375, 1–4 (2019).

doi: 10.1016/j.taap.2019.05.006

Singh, R. K. et al. Excess histone levels mediate cytotoxicity via multiple mechanisms. Cell Cycle 9, 4236–4244 (2010).

pubmed: 20948314 pmcid: 3055206 doi: 10.4161/cc.9.20.13636

Marzluff, W. F. & Koreski, K. P. Birth and death of histone mRNAs. Trends Genet. 33, 745–759 (2017).

pubmed: 28867047 pmcid: 5645032 doi: 10.1016/j.tig.2017.07.014

Zheng, L. et al. Phosphorylation of stem-loop binding protein (SLBP) on two threonines triggers degradation of SLBP, the sole cell cycle-regulated factor required for regulation of histone mRNA processing, at the end of S phase. Mol. Cell. Biol. 23, 1590–1601 (2003).

pubmed: 12588979 pmcid: 151715 doi: 10.1128/MCB.23.5.1590-1601.2003

Mitrea, D. M. & Kriwacki, R. W. Phase separation in biology; functional organization of a higher order. Cell Commun. Signal. 14, 1 (2016).

pubmed: 26727894 pmcid: 4700675 doi: 10.1186/s12964-015-0125-7

Mukundan, B. & Ansari, A. Srb5/Med18-mediated termination of transcription is dependent on gene looping. J. Biol. Chem. 288, 11384–11394 (2013).

pubmed: 23476016 pmcid: 3630880 doi: 10.1074/jbc.M112.446773

Erb, M. A. et al. Transcription control by the ENL YEATS domain in acute leukaemia. Nature 543, 270–274 (2017).

pubmed: 28241139 pmcid: 5497220 doi: 10.1038/nature21688

Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281–2308 (2013).

pubmed: 24157548 pmcid: 3969860 doi: 10.1038/nprot.2013.143

Lens, Z. et al. Solution structure of the N-terminal domain of mediator subunit MED26 and molecular characterization of its interaction with EAF1 and TAF7. J. Mol. Biol. 429, 3043–3055 (2017).

pubmed: 28893534 doi: 10.1016/j.jmb.2017.09.001 pmcid: 28893534

Starck, S. R. et al. Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I. Science 336, 1719–1723 (2012).

pubmed: 22745432 doi: 10.1126/science.1220270 pmcid: 22745432

Natsume, T., Kiyomitsu, T., Saga, Y. & Kanemaki, M. T. Rapid protein depletion in human cells by auxin-inducible degron tagging with short homology donors. Cell Rep. 15, 210–218 (2016).

pubmed: 27052166 doi: 10.1016/j.celrep.2016.03.001 pmcid: 27052166

Dignam, J. D., Martin, P. L., Shastry, B. S. & Roeder, R. G. Eukaryotic gene transcription with purified components. Methods Enzymol. 101, 582–598 (1983).

pubmed: 6888276 doi: 10.1016/0076-6879(83)01039-3 pmcid: 6888276

Florens, L. & Washburn, M. P. Proteomic analysis by multidimensional protein identification technology. Methods Mol. Biol. 328, 159–175 (2006).

pubmed: 16785648 pmcid: 16785648

Washburn, M. P., Wolters, D. & Yates, J. R. 3rd Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat. Biotechnol. 19, 242–247 (2001).

pubmed: 11231557 doi: 10.1038/85686 pmcid: 11231557

Eng, J. K., McCormack, A. L. & Yates, J. R. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. J. Am. Soc. Mass Spectrom. 5, 976–989 (1994).

pubmed: 24226387 doi: 10.1016/1044-0305(94)80016-2 pmcid: 24226387

Xu, T. et al. ProLuCID: an improved SEQUEST-like algorithm with enhanced sensitivity and specificity. J. Proteom. 129, 16–24 (2015).

doi: 10.1016/j.jprot.2015.07.001

Tabb, D. L., McDonald, W. H. & Yates, J. R. 3rd DTASelect and Contrast: tools for assembling and comparing protein identifications from shotgun proteomics. J. Proteome Res. 1, 21–26 (2002).

pubmed: 12643522 pmcid: 2811961 doi: 10.1021/pr015504q

Paoletti, A. C. & Washburn, M. P. Quantitation in proteomic experiments utilizing mass spectrometry. Biotechnol. Genet. Eng. Rev. 22, 1–19 (2006).

pubmed: 18476323 doi: 10.1080/02648725.2006.10648062 pmcid: 18476323

Zhang, Y., Wen, Z., Washburn, M. P. & Florens, L. Refinements to label free proteome quantitation: how to deal with peptides shared by multiple proteins. Anal. Chem. 82, 2272–2281 (2010).

pubmed: 20166708 doi: 10.1021/ac9023999 pmcid: 20166708

Zybailov, B. et al. Statistical analysis of membrane proteome expression changes in Saccharomyces cerevisiae. J. Proteome Res. 5, 2339–2347 (2006).

pubmed: 16944946 doi: 10.1021/pr060161n pmcid: 16944946

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 doi: 10.1038/nprot.2016.086

Kwak, H., Fuda, N. J., Core, L. J. & Lis, J. T. Precise maps of RNA polymerase reveal how promoters direct initiation and pausing. Science 339, 950–953 (2013).

pubmed: 23430654 pmcid: 3974810 doi: 10.1126/science.1229386