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RNA demethylation increases the yield and biomass of rice and potato plants in field trials



Abstract

RNA N6-methyladenosine (m6A) modifications are essential in plants. Here, we show that transgenic expression of the human RNA demethylase FTO in rice caused a more than threefold increase in grain yield under greenhouse conditions. In field trials, transgenic expression of FTO in rice and potato caused ~50% increases in yield and biomass. We demonstrate that the presence of FTO stimulates root meristem cell proliferation and tiller bud formation and promotes photosynthetic efficiency and drought tolerance but has no effect on mature cell size, shoot meristem cell proliferation, root diameter, plant height or ploidy. FTO mediates substantial m6A demethylation (around 7% of demethylation in poly(A) RNA and around 35% decrease of m6A in non-ribosomal nuclear RNA) in plant RNA, inducing chromatin openness and transcriptional activation. Therefore, modulation of plant RNA m6A methylation is a promising strategy to dramatically improve plant growth and crop yield.

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Data availability

m6A-seq and quantitative RNA-seq data generated by this study were deposited in the GEO database under the accession number GSE135549. Source data are provided with this paper.



References



  1. 1.

Godfray, H. C. J. et al. Food security: the challenge of feeding 9 billion people. Science 327, 812–818 (2010).

  1. 2.

Bailey-Serres, J., Parker, J. E., Ainsworth, E. A., Oldroyd, G. E. D. & Schroeder, J. I. Genetic strategies for improving crop yields. Nature 575, 109–118 (2019).

  1. 3.

Vaeck, M. et al. Transgenic plants protected from insect attack. Nature 328, 33–37 (1987).

  1. 4.

Rao, V. S. Transgenic Herbicide Resistance in Plants (CRC Press, 2014).

  1. 5.

Wang, J. et al. A single transcription factor promotes both yield and immunity in rice. Science 361, 1026–1028 (2018).

  1. 6.

Wang, Y. & Li, J. Molecular basis of plant architecture. Annu. Rev. Plant Biol. 59, 253–279 (2008).

  1. 7.

Miura, K. et al. OsSPL14 promotes panicle branching and higher grain productivity in rice. Nat. Genet. 42, 545–549 (2010).

  1. 8.

Li, S. et al. Modulating plant growth—metabolism coordination for sustainable agriculture. Nature 560, 595–600 (2018).

  1. 9.

South, P. F., Cavanagh, A. P., Liu, H. W. & Ort, D. R. Synthetic glycolate metabolism pathways stimulate crop growth and productivity in the field. Science 363, eaat9077 (2019).

  1. 10.

Frye, M., Harada, B. T., Behm, M. & He, C. RNA modifications modulate gene expression during development. Science 361, 1346–1349 (2018).

  1. 11.

Dominissini, D. et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485, 201–206 (2012).

  1. 12.

Meyer, K. D. et al. Comprehensive analysis of mRNA methylation reveals enrichment in 3′UTRs and near stop codons. Cell 149, 1635–1646 (2012).

  1. 13.

Geula, S. et al. m6A mRNA methylation facilitates resolution of naive pluripotency toward differentiation. Science 347, 1002–1006 (2015).

  1. 14.

Frayling, T. M. et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889–894 (2007).

  1. 15.

Jia, G. et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7, 885–887 (2011).

  1. 16.

Mauer, J. et al. Reversible methylation of m6Am in the 5′ cap controls mRNA stability. Nature 541, 371–375 (2017).

  1. 17.

Wei, J. et al. Differential m6A, m6Am, and m1A demethylation mediated by FTO in the cell nucleus and cytoplasm. Mol. Cell 71, 973–985 (2018).

  1. 18.

Mauer, J. et al. FTO controls reversible m6Am RNA methylation during snRNA biogenesis. Nat. Chem. Biol. 15, 340–347 (2019).

  1. 19.

Li, Z. et al. FTO plays an oncogenic role in acute myeloid leukemia as a N6-methyladenosine RNA demethylase. Cancer Cell 31, 127–141 (2017).

  1. 20.

Zhong, S. et al. MTA is an Arabidopsis messenger RNA adenosine methylase and interacts with a homolog of a sex-specific splicing factor. Plant Cell 20, 1278–1288 (2008).

  1. 21.

Bodi, Z. et al. Adenosine methylation in Arabidopsis mRNA is associated with the 3′ end and reduced levels cause developmental defects. Front. Plant Sci. 3, 48 (2012).

  1. 22.

Shen, L. et al. N6-methyladenosine RNA modification regulates shoot stem cell fate in Arabidopsis. Dev. Cell 38, 186–200 (2016).

  1. 23.

Růžička, K. et al. Identification of factors required for m6A mRNA methylation in Arabidopsis reveals a role for the conserved E3 ubiquitin ligase HAKAI. New Phytol. 215, 157–172 (2017).

  1. 24.

Zhang, F. et al. The subunit of RNA N6-methyladenosine methyltransferase OsFIP regulates early degeneration of microspores in rice. PLoS Genet. 15, e1008120 (2019).

  1. 25.

Zheng, G. et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 49, 18–29 (2013).

  1. 26.

Duan, H. C. et al. ALKBH10B is an RNA N6-methyladenosine demethylase affecting Arabidopsis floral transition. Plant Cell 29, 2995–3011 (2017).

  1. 27.

Martinez-Perez, M. et al. Arabidopsis m6A demethylase activity modulates viral infection of a plant virus and the m6A abundance in its genomic RNAs. Proc. Natl Acad. Sci. USA 114, 10755–10760 (2017).

  1. 28.

Scutenaire, J. et al. The YTH domain protein ECT2 is an m6A reader required for normal trichome branching in Arabidopsis. Plant Cell 30, 986–1005 (2018).

  1. 29.

Wei, L. H. et al. The m6A reader ECT2 controls trichome morphology by affecting mRNA stability in Arabidopsis. Plant Cell 30, 968–985 (2018).

  1. 30.

Arribas-Hernández, L. et al. An m6A-YTH module controls developmental timing and morphogenesis in Arabidopsis. Plant Cell 30, 952–967 (2018).

  1. 31.

Arribas-Hernández, L. et al. Recurrent requirement for the m6A-ECT2/ECT3/ECT4 axis in the control of cell proliferation during plant organogenesis. Development 147, dev189134 (2020).

  1. 32.

Hou, Y. et al. CPSF30-L-mediated recognition of mRNA m6A modification controls alternative polyadenylation of nitrate signaling-related gene transcripts in Arabidopsis. Mol. Plant 14, 688–699 (2021).

  1. 33.

Song, P. et al. Arabidopsis N6-methyladenosine reader CPSF30-L recognizes FUE signal to control polyadenylation site choice in liquid-like nuclear body. Mol. Plant 14, 571–587 (2021).

  1. 34.

Wu, J., Peled-Zehavi, H. & Galili, G. The m6A reader ECT2 post-transcriptionally regulates proteasome activity in Arabidopsis. New Phytol. 228, 151–162 (2020).

  1. 35.

Li, X. et al. Control of tillering in rice. Nature 422, 618–621 (2003).

  1. 36.

Pirasteh-Anosheh, H., Saed-Moucheshi, A., Pakniyat, H. & Pessarakli, M. Stomatal responses to drought stress. in Water Stress and Crop Plants: A Sustainable Approach 24–40 (Wiley, 2016).

  1. 37.

Akichika, S. et al. Cap-specific terminal N6-methylation of RNA by an RNA polymerase II-associated methyltransferase. Science 363, eaav0080 (2019).

  1. 38.

Liu, J. et al. N6-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription. Science 367, 580–586 (2020).

  1. 39.

Jachowicz, J. W. et al. LINE-1 activation after fertilization regulates global chromatin accessibility in the early mouse embryo. Nat. Genet. 49, 1502–1510 (2017).

  1. 40.

Percharde, M. et al. A LINE1–nucleolin partnership regulates early development and ESC identity. Cell 174, 391–405 (2018).

  1. 41.

Sattler, M. C., Carvalho, C. R. & Clarindo, W. R. The polyploidy and its key role in plant breeding. Planta 243, 281–296 (2016).

  1. 42.

Wang, X. et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 505, 117–120 (2014).

  1. 43.

Chelmicki, T. et al. m6A RNA methylation regulates the fate of endogenous retroviruses. Nature 591, 312–316 (2021).

  1. 44.

Xu, W. et al. METTL3 regulates heterochromatin in mouse embryonic stem cells. Nature 591, 317–321 (2021).

  1. 45.

Liu, J. et al. The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity. Nature 591, 322–326 (2021).

  1. 46.

Toki, S. et al. Early infection of scutellum tissue with Agrobacterium allows high-speed transformation of rice. Plant J. 47, 969–976 (2006).

  1. 47.

Yang, L. et al. Estimating the copy number of transgenes in transformed rice by real-time quantitative PCR. Plant Cell Rep. 23, 759–763 (2005).

  1. 48.

Ding, J. et al. Validation of a rice specific gene, sucrose phosphate synthase, used as the endogenous reference gene for qualitative and real-time quantitative PCR detection of transgenes. J. Agric. Food Chem. 52, 3372–3377 (2004).

  1. 49.

Chetty, V. J., Narváez-Vásquez, J. & Orozco-Cárdenas, M. L. Potato (Solanum tuberosum L.). In Agrobacterium Protocols 3rd edn, Vol. 2 (ed Wang, K.), 85–96 (Springer, 2015).

  1. 50.

Witte, C. P., Tiller, S., Isidore, E., Davies, H. V. & Taylor, M. A. Analysis of two alleles of the urease gene from potato: polymorphisms, expression, and extensive alternative splicing of the corresponding mRNA. J. Exp. Bot. 56, 91–99 (2005).

  1. 51.

Ambavaram, M. M. et al. Coordinated regulation of photosynthesis in rice increases yield and tolerance to environmental stress. Nat. Commun. 5, 5302 (2014).

  1. 52.

Wen, Z., Li, H., Shen, J. & Rengel, Z. Maize responds to low shoot P concentration by altering root morphology rather than increasing root exudation. Plant Soil 416, 377–389 (2017).

  1. 53.

Ioio, R. D. et al. A genetic framework for the control of cell division and differentiation in the root meristem. Science 322, 1380–1384 (2008).

  1. 54.

Yang, F. et al. A maize glutaredoxin gene, abphyl2, regulates shoot meristem size and phyllotaxy. Plant Cell 27, 121–131 (2015).

  1. 55.

Zhong, R., Taylor, J. J. & Ye, Z. H. Disruption of interfascicular fiber differentiation in an Arabidopsis mutant. Plant Cell 9, 2159–2170 (1997).

  1. 56.

Xu, L. et al. ABNORMAL INFLORESCENCE MERISTEM1 functions in salicylic acid biosynthesis to maintain proper reactive oxygen species levels for root meristem activity in rice. Plant Cell 29, 560–574 (2017).

  1. 57.

Zhou, C. et al. Identification and analysis of adenine N6-methylation sites in the rice genome. Nat. Plants 4, 554–563 (2018).

  1. 58.

Saleh, A., Alvarez-Venegas, R. & Avramova, Z. An efficient chromatin immunoprecipitation (ChIP) protocol for studying histone modifications in Arabidopsis plants. Nat. Protoc. 3, 1018–1025 (2008).

  1. 59.

Yang, L., Wang, Z. & Hua, J. Measuring cell ploidy level in Arabidopsis thaliana by flow cytometry. Methods Mol. Biol. 1991, 101–106 (2019).

  1. 60.

Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 17, 10–12 (2011).

  1. 61.

Kim, D., Langmead, B. & Salzberg, S. L. HISAT: a fast spliced aligner with low memory requirements. Nat. Methods 12, 357–360 (2015).

  1. 62.

Cui, X., Meng, J., Zhang, S., Chen, Y. & Huang, Y. A novel algorithm for calling mRNA m6A peaks by modeling biological variances in MeRIP-seq data. Bioinformatics 32, i378–i385 (2016).

  1. 63.

Liao, Y., Smyth, G. K. & Shi, W. The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote. Nucleic Acids Res. 41, e108 (2013).

  1. 64.

Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576–589 (2010).

  1. 65.

Gautier, L., Cope, L., Bolstad, B. M. & Irizarry, R. A. Affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20, 307–315 (2004).

  1. 66.

Loven, J. et al. Revisiting global gene expression analysis. Cell 151, 476–482 (2012).

  1. 67.

Tian, T. et al. AgriGO v2.0: a GO analysis toolkit for the agricultural community, 2017 update. Nucleic Acids Res. 45, W122–W129 (2017).

  1. 68.

Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).

  1. 69.

Merico, D., Isserlin, R., Stueker, O., Emili, A. & Bader, G. D. Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS ONE 5, e13984 (2010).


Acknowledgements

We thank Y. Wang for paraffin embedding station support, C. Xu for microtome support and X. Meng and J. Wang for assistance during field work. This work was supported by the National Basic Research Program of China (2019YFA0802201 and 2017YFA0505201 to G.J.), the National Natural Science Foundation of China (21822702, 21820102008, 92053109 and 21432002 to G.J.), the Beijing Natural Science Foundation (Z200010 to G.J.), EpiPlanta Biotech Ltd. (to G.J.), the Beijing Advanced Innovation Center for Genomics at Peking University (to G.J.) and the Zhong Ziyi Education Foundation (to C.H.). C.H. is a Howard Hughes Medical Institute Investigator.


Author information


Author notes


These authors contributed equally: Qiong Yu, Shun Liu.

Affiliations


Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China

Qiong Yu, Yu Xiao, Shasha Zhang, Xueping Wang, Yingying Xu, Junbo Yang, Jun Tang, Hong-Chao Duan, Lian-Huan Wei, Qian Tang, Chunling Wang, Wutong Zhang, Ye Wang, Peizhe Song, Qiang Lu, Wei Zhang, Shunqing Dong & Guifang Jia


Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA

Shun Liu, Jiangbo Wei & Chuan He


Howard Hughes Medical Institute, Chicago, IL, USA

Shun Liu, Jiangbo Wei & Chuan He


State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering/Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang, China

Lu Yu & Baoan Song


State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, The Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing, China

Hong Yu


School of Life Sciences, Jiangsu University, Zhenjiang, China

Yulong Li


College of Life Sciences, Tianjin Normal University, Tianjin, China

Haiyan Zhang


Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA

Chuan He


National Engineering Research Center of Pesticide, Nankai University, Tianjin, China

Guifang Jia

Contributions

G.J. and C.H. conceived the original idea and designed original studies. Q.Y. performed most experiments with help from Y.L., Y. Xiao., S.Z., X.W., Y. Xu, Y.L., J.Y., J.T., H.-C.D., L.-H.W., Q.T., C.W., Wutong Zhang, Y.W., P.S., Q.L., Wei Zhang, S.D., H.Y., H.Z. and B.S. S.L. performed most computational analysis with help from J.W. G.J. and C.H. wrote the manuscript with input from Q.Y. and S.L.

Corresponding authors

Correspondence to Baoan Song or Chuan He or Guifang Jia.


Ethics declarations


Competing interests

A patent application has been filed by EpiPlanta Biotech Ltd. for the technology disclosed in this publication. C.H. is a scientific founder and a member of the scientific advisory board of Accent Therapeutics.


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Peer review information Nature Biotechnology thanks Brian Gregory and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Cite this article

Yu, Q., Liu, S., Yu, L. et al. RNA demethylation increases the yield and biomass of rice and potato plants in field trials. Nat Biotechnol (2021). https://doi.org/10.1038/s41587-021-00982-9


Received: 10 September 2019


Accepted: 11 June 2021


Published: 22 July 2021


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