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Coupling of histone methylation and RNA processing by the nuclear mRNA cap-binding complex

Nature Plants volume 2, Article number: 16015 (2016) Cite this article

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Abstract

In eukaryotes, genes are transcribed into pre-mRNAs that are subsequently processed into mature mRNAs by adding a 5′-cap and a 3′-polyA tail and splicing introns. Pre-mRNA processing involves their binding proteins and processing factors, whereas gene transcription often involves chromatin modifiers. It has been unclear how the factors involved in chromatin modifications and RNA processing function in concert to control mRNA production. Here, we show that in Arabidopsis thaliana, the evolutionarily conserved nuclear mRNA cap-binding complex (CBC) forms multi-protein complexes with a conserved histone 3 lysine 4 (H3K4) methyltransferase complex called COMPASS-like and a histone 3 lysine 36 (H3K36) methyltransferase to integrate active histone methylations with co-transcriptional mRNA processing and cap preservation, leading to a high level of mature mRNA production. We further show that CBC is required for H3K4 and H3K36 trimethylation, and the histone methyltransferases are required for CBC-mediated mRNA cap preservation and efficient pre-mRNA splicing at their target loci, suggesting that these factors are functionally interdependent. Our study reveals novel roles for histone methyltransferases in RNA-processing-related events and provides mechanistic insights into how the ‘downstream’ RNA CBC controls eukaryotic gene transcription.

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Figure 1: CBP20 associates with EFS and the COMPASS-like subunits.
Figure 2: CBP20 is required for ASH2R function, H3K4me3 and H3K36me3 at the FLC locus.
Figure 3: Analysis of capped and uncapped mature mRNAs.
Figure 4: Analysis of FLC splicing and Pol II occupancy at FLC.
Figure 5: CBC, COMPASS-like and EFS co-regulate various genes in Arabidopsis.

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References

  1. Shandilya, J. & Roberts, S. G. The transcription cycle in eukaryotes: from productive initiation to RNA polymerase II recycling. Biochim. Biophys. Acta 1819, 391–400 (2012).

    Article  CAS  Google Scholar 

  2. Dieci, G. & Sentenac, A. Detours and shortcuts to transcription reinitiation. Trends Biochem. Sci. 28, 202–209 (2003).

    Article  CAS  Google Scholar 

  3. Ruthenburg, A. J., Allis, C. D. & Wysocka, J. Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. Mol. Cell 25, 15–30 (2007).

    Article  CAS  Google Scholar 

  4. Shilatifard, A. Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr. Opin. Cell Biol. 20, 341–348 (2008).

    Article  CAS  Google Scholar 

  5. Lauberth, S. M. et al. H3K4me3 interactions with TAF3 regulate preinitiation complex assembly and selective gene activation. Cell 152, 1021–1036 (2013).

    Article  CAS  Google Scholar 

  6. Ding, Y. et al. ATX1-generated H3K4me3 is required for efficient elongation of transcription, not initiation, at ATX1-regulated genes. PLoS Genet. 8, e1003111 (2012).

    Article  Google Scholar 

  7. Wagner, E. J. & Carpenter, P. B. Understanding the language of Lys36 methylation at histone H3. Nature Rev. Mol. Cell Biol. 13, 115–126 (2012).

    Article  CAS  Google Scholar 

  8. Xu, L. et al. Di- and tri- but not monomethylation on histone H3 lysine 36 marks active transcription of genes involved in flowering time regulation and other processes in Arabidopsis thaliana. Mol. Cell Biol. 28, 1348–1360 (2008).

    Article  CAS  Google Scholar 

  9. Kim, S. Y. et al. Establishment of the vernalization-responsive, winter-annual habit in Arabidopsis requires a putative histone H3 methyl transferase. Plant Cell 17, 3301–3310 (2005).

    Article  CAS  Google Scholar 

  10. Sims, R. J. 3rd et al. Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing. Mol. Cell 28, 665–676 (2007).

    Article  CAS  Google Scholar 

  11. Spies, N., Nielsen, C. B., Padgett, R. A. & Burge, C. B. Biased chromatin signatures around polyadenylation sites and exons. Mol. Cell 36, 245–254 (2009).

    Article  CAS  Google Scholar 

  12. Gunderson, F. Q., Merkhofer, E. C. & Johnson, T. L. Dynamic histone acetylation is critical for cotranscriptional spliceosome assembly and spliceosomal rearrangements. Proc. Natl Acad. Sci. USA 108, 2004–2009 (2011).

    Article  CAS  Google Scholar 

  13. Zhang, Z. et al. USP49 deubiquitinates histone H2B and regulates cotranscriptional pre-mRNA splicing. Genes Dev. 27, 1581–1595 (2013).

    Article  CAS  Google Scholar 

  14. Calero, G. et al. Structural basis of m7GpppG binding to the nuclear cap-binding protein complex. Nature Struct. Biol. 9, 912–917 (2002).

    Article  CAS  Google Scholar 

  15. Jurado, A. R., Tan, D., Jiao, X., Kiledjian, M. & Tong, L. Structure and function of pre-mRNA 5′-end capping quality control and 3′-end processing. Biochemistry 53, 1882–1898 (2014).

    Article  CAS  Google Scholar 

  16. Lidschreiber, M., Leike, K. & Cramer, P. Cap completion and C-terminal repeat domain kinase recruitment underlie the initiation-elongation transition of RNA Polymerase II. Mol Cell Biol. 33, 3805–3816 (2013).

    Article  CAS  Google Scholar 

  17. Orphanides, G. & Reinberg, D. A unified theory of gene expression. Cell 108, 439–451 (2002).

    Article  CAS  Google Scholar 

  18. Hugouvieux, V., Kwak, J. M. & Schroeder, J. I. An mRNA cap binding protein, ABH1, modulates early abscisic acid signal transduction in Arabidopsis. Cell 106, 477–487 (2001).

    Article  CAS  Google Scholar 

  19. Kmieciak, M., Simpson, C. G., Lewandowska, D., Brown, J. W. & Jarmolowski, A. Cloning and characterization of two subunits of Arabidopsis thaliana nuclear Cap-Binding Complex. Gene 283, 171–183 (2002).

    Article  CAS  Google Scholar 

  20. Wong, C. M., Qiu, H., Hu, C., Dong, J. & Hinnebusch, A. G. Yeast Cap-Binding Complex impedes recruitment of cleavage factor IA to weak termination sites. Mol. Cell Biol. 27, 6520–6531 (2007).

    Article  CAS  Google Scholar 

  21. Gornemann, J., Kotovic, K. M., Hujer, K. & Neugebauer, K. M. Cotranscriptional spliceosome assembly occurs in a stepwise fashion and requires the Cap-Binding Complex. Mol. Cell 19, 53–63 (2005).

    Article  Google Scholar 

  22. Izaurralde, E. et al. A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell 78, 657–668 (1994).

    Article  CAS  Google Scholar 

  23. Jiang, D., Kong, N. C., Gu, X., Li, Z. & He, Y. Arabidopsis COMPASS-like complexes mediate histone H3 lysine-4 trimethylation to control floral transition and plant development. PLoS Genet. 7, e1001330 (2011).

    Article  CAS  Google Scholar 

  24. Zhao, Z., Yu, Y., Meyer, D., Wu, C. & Shen, W. H. Prevention of early flowering by expression of FLOWERING LOCUS C requires methylation of histone H3 K36. Nature Cell Biol. 7, 1256–1260 (2005).

    Article  Google Scholar 

  25. Bezerra, I. C., Michaels, S. D., Schomburg, F. M. & Amasino, R. M. Lesions in the mRNA cap-binding gene ABA HYPERSENSITIVE 1 suppress FRIGIDA-mediated delayed flowering in Arabidopsis. Plant J. 40, 112–119 (2004).

    Article  CAS  Google Scholar 

  26. Geraldo, N., Baurle, I., Kidou, S., Hu, X. & Dean, C. FRIGIDA delays flowering in Arabidopsis via a cotranscriptional mechanism involving direct interaction with the nuclear Cap-Binding Complex. Plant Physiol. 150, 1611–1618 (2009).

    Article  CAS  Google Scholar 

  27. Kierzkowski, D. et al. The Arabidopsis CBP20 targets the Cap-Binding Complex to the nucleus, and is stabilized by CBP80. Plant J. 59, 814–825 (2009).

    Article  Google Scholar 

  28. Jiang, D., Gu, X. & He, Y. Establishment of the winter-annual growth habit via FRIGIDA-mediated histone methylation at FLOWERING LOCUS C in Arabidopsis. Plant Cell 21, 1733–1746 (2009).

    Article  CAS  Google Scholar 

  29. Kim, S. et al. Two cap-binding proteins CBP20 and CBP80 are involved in processing primary microRNAs. Plant Cell Physiol. 49, 1634–1644 (2008).

    Article  CAS  Google Scholar 

  30. Ko, J. H. et al. Growth habit determination by the balance of histone methylation activities in Arabidopsis. EMBO J. 29, 3208–3215 (2010).

    Article  CAS  Google Scholar 

  31. Cao, Y., Dai, Y., Cui, S. & Ma, L. Histone H2B monoubiquitination in the chromatin of FLOWERING LOCUS C regulates flowering time in Arabidopsis. Plant Cell 20, 2586–2602 (2008).

    Article  CAS  Google Scholar 

  32. Xu, L. et al. The E2 ubiquitin-conjugating enzymes, AtUBC1 and AtUBC2, play redundant roles and are involved in activation of FLC expression and repression of flowering in Arabidopsis thaliana. Plant J. 57, 279–288 (2008).

    Article  Google Scholar 

  33. Papp, I., Mur, L. A., Dalmadi, A., Dulai, S. & Koncz, C. A mutation in the CAP-BINDING PROTEIN 20 gene confers drought tolerance to Arabidopsis. Plant Mol. Biol. 55, 679–686 (2004).

    Article  CAS  Google Scholar 

  34. Kolasinska-Zwierz, P. et al. Differential chromatin marking of introns and expressed exons by H3K36me3. Nat Genet. 41, 376–381 (2009).

    Article  CAS  Google Scholar 

  35. Jiao, Y., Riechmann, J. L. & Meyerowitz, E. M. Transcriptome-wide analysis of uncapped mRNAs in Arabidopsis reveals regulation of mRNA degradation. Plant Cell 20, 2571–2585 (2008).

    Article  CAS  Google Scholar 

  36. Pien, S. et al. ARABIDOPSIS TRITHORAX1 dynamically regulates FLOWERING LOCUS C activation via histone H3 lysine-4 trimethylation. Plant Cell 20, 580–588 (2008).

    Article  CAS  Google Scholar 

  37. Lee, I., Michaels, S. D., Masshardt, A. S. & Amasino, R. M. The late-flowering phenotype of FRIGIDA and LUMINIDEPENDENS is suppressed in the Landsberg erecta strain of Arabidopsis. Plant J. 6, 903–909 (1994).

    Article  CAS  Google Scholar 

  38. Oh, S., Park, S. & van Nocker, S. Genic and global functions for Paf1C in chromatin modification and gene expression in Arabidopsis. PLoS Genet. 4, e1000077 (2008).

    Article  Google Scholar 

  39. Zhang, X., Bernatavichute, Y. V., Cokus, S., Pellegrini, M. & Jacobsen, S. E. Genome-wide analysis of mono-, di- and trimethylation of histone H3 lysine 4 in Arabidopsis thaliana. Genome Biol. 10, R62 (2009).

    Article  Google Scholar 

  40. Valencia-Morales Mdel, P., Camas-Reyes, J. A., Cabrera-Ponce, J. L. & Alvarez-Venegas, R. The Arabidopsis thaliana SET-domain-containing protein ASHH1/SDG26 interacts with itself and with distinct histone lysine methyltransferases. J. Plant Res. 125, 679–692 (2012).

    Article  Google Scholar 

  41. Krogan, N. J. et al. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA Polymerase II. Mol. Cell Biol. 23, 4207–4218 (2003).

    Article  CAS  Google Scholar 

  42. Ng, H. H., Robert, F., Young, R. A. & Struhl, K. Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol. Cell 11, 709–719 (2003).

    Article  CAS  Google Scholar 

  43. Wood, A., Schneider, J., Dover, J., Johnston, M. & Shilatifard, A. The Paf1 complex is essential for histone monoubiquitination by the Rad6-Bre1 complex, which signals for histone methylation by COMPASS and Dot1p. J. Biol. Chem. 278, 34739–34742 (2003).

    Article  CAS  Google Scholar 

  44. Hossain, M. A., Chung, C., Pradhan, S. K. & Johnson, T. L. The yeast Cap-Binding Complex modulates transcription factor recruitment and establishes proper histone H3K36 trimethylation during active transcription. Mol. Cell Biol. 33, 785–799 (2013).

    Article  CAS  Google Scholar 

  45. Dias, S. M., Wilson, K. F., Rojas, K. S., Ambrosio, A. L. & Cerione, R. A. The molecular basis for the regulation of the Cap-Binding Complex by the importins. Nature Struct. Mol. Biol. 16, 930–937 (2009).

    Article  CAS  Google Scholar 

  46. Michaels, S. & Amasino, R. FLOWERING LOCUS C encodes a novel MADS domain protein that acts as a repressor of flowering. Plant Cell 11, 949–956 (1999).

    Article  CAS  Google Scholar 

  47. He, Y., Doyle, M. R. & Amasino, R. M. PAF1-complex-mediated histone methylation of FLOWERING LOCUS C chromatin is required for the vernalization-responsive, winter-annual habit in Arabidopsis. Genes Dev. 18, 2774–2784 (2004).

    Article  CAS  Google Scholar 

  48. Quinlivan, E. P. & Gregory, J. F. 3rd . DNA digestion to deoxyribonucleoside: a simplified one-step procedure. Anal Biochem. 373, 383–385 (2008).

    Article  CAS  Google Scholar 

  49. Wang, Y., Gu, X., Yuan, W., Schmitz, R. J. & He, Y. Photoperiodic control of the floral transition through a distinct polycomb repressive complex. Dev. Cell 28, 727–736 (2014).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank A. Jarmolowski for kindly providing the cbp20 seeds, Stanton B. Gelvin for BiFC vectors, and Heng Zhang for high-throughput sequencing of ChIP samples. This work was supported by funding from the Chinese Academy of Sciences and by a grant from the Singapore Ministry of Education (AcRF Tier 2; MOE2013-T2-1-025) to Y.H.

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Author notes

  1. Danhua Jiang

    Present address: †Present address: Gregor Mendel Institute of Molecular Plant Biology, 1030 Vienna, Austria,

  2. Zicong Li and Danhua Jiang: These authors contributed equally to this work.

Authors and Affiliations

  1. Shanghai Center for Plant Stress Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 201602, China

    Zicong Li, Xing Fu, Xiao Luo, Renyi Liu & Yuehui He

  2. Department of Biological Sciences and Temasek Life Sciences Laboratory, National University of Singapore, 117543 Singapore, Singapore

    Zicong Li, Danhua Jiang & Yuehui He

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  1. Zicong Li
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Contributions

Y.H. conceived the research. Z.L., D.J. and X.L. conducted the experiments, Z.L., D.J., Y.H., X.F., X.L. and R.L. carried out data analyses. Y.H. and Z.L. wrote the paper.

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Correspondence to Yuehui He.

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Li, Z., Jiang, D., Fu, X. et al. Coupling of histone methylation and RNA processing by the nuclear mRNA cap-binding complex. Nature Plants 2, 16015 (2016). https://doi.org/10.1038/nplants.2016.15

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