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m6A mRNA methylation in human brain is disrupted in Lewy body disorders (2023)
Journal Article
Martinez De La Cruz, B., Gell, C., Markus, R., Macdonald, I., Fray, R., & Knight, H. M. (2023). m6A mRNA methylation in human brain is disrupted in Lewy body disorders. Neuropathology and Applied Neurobiology, 49(1), Article e12885. https://doi.org/10.1111/nan.12885

N6-methyladenosine modification of RNA (m6A) regulates translational control which may influence neuronal dysfunction underlying neurodegenerative diseases. Using microscopy and a machine learning approach, we performed cellular profiling of m6A-RNA... Read More about m6A mRNA methylation in human brain is disrupted in Lewy body disorders.

The importance of m6A topology in chicken embryo mRNA: a precise mapping of m6A at the conserved chicken β-actin zipcode (2023)
Journal Article
Baron, F., Zhang, M., Archer, N., Bellows, E., Knight, H. M., Welham, S., …Bodi, Z. (2023). The importance of m6A topology in chicken embryo mRNA: a precise mapping of m6A at the conserved chicken β-actin zipcode. RNA, 29(6), 777-789. https://doi.org/10.1261/rna.079615.123

N6-methyladenosine (m6A) in mRNA regulates almost every stage in the mRNA life cycle, and the development of methodologies for the high-throughput detection of methylated sites in mRNA using m6A-specific methylated RNA immunoprecipitation with next-g... Read More about The importance of m6A topology in chicken embryo mRNA: a precise mapping of m6A at the conserved chicken β-actin zipcode.

Clinical and molecular significance of the RNA m6A methyltransferase complex in prostate cancer (2023)
Journal Article
Lothion-Roy, J., Haigh, D. B., Harris, A. E., Metzler, V. M., Alsaleem, M., Toss, M. S., …Woodcock, C. L. (2023). Clinical and molecular significance of the RNA m6A methyltransferase complex in prostate cancer. Frontiers in Genetics, 13, Article 1096071. https://doi.org/10.3389/fgene.2022.1096071

N6-methyladenosine (m6A) is the most abundant internal mRNA modification and is dynamically regulated through distinct protein complexes that methylate, demethylate, and/or interpret the m6A modification. These proteins, and the m6A modification, are... Read More about Clinical and molecular significance of the RNA m6A methyltransferase complex in prostate cancer.

Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer (2022)
Journal Article
Harris, A. E., Metzler, V. M., Lothion-Roy, J., Varun, D., Woodcock, C. L., Haigh, D. B., …Jeyapalan, J. N. (2022). Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer. Frontiers in Endocrinology, 13, Article 1006101. https://doi.org/10.3389/fendo.2022.1006101

Androgen deprivation therapies (ADTs) are important treatments which inhibit androgen-induced prostate cancer (PCa) progression by either preventing androgen biosynthesis (e.g. abiraterone) or by antagonizing androgen receptor (AR) function (e.g. bic... Read More about Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer.

The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer (2022)
Journal Article
Haigh, D. B., Woodcock, C. L., Lothion-Roy, J., Harris, A. E., Metzler, V. M., Persson, J. L., …Mongan, N. P. (2022). The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer. Cancers, 14(20), Article 5148. https://doi.org/10.3390/cancers14205148

Prostate cancer (PCa) is a leading cause of cancer-related deaths and is driven by aberrant androgen receptor (AR) signalling. For this reason, androgen deprivation therapies (ADTs) that suppress androgen-induced PCa progression either by preventing... Read More about The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer.

CMTr cap-adjacent 2′-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses (2022)
Journal Article
Haussmann, I. U., Wu, Y., Nallasivan, M. P., Archer, N., Bodi, Z., Hebenstreit, D., …Soller, M. (2022). CMTr cap-adjacent 2′-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses. Nature Communications, 13(1), Article 1209. https://doi.org/10.1038/s41467-022-28549-5

Cap-adjacent nucleotides of animal, protist and viral mRNAs can be O-methylated at the 2`position of the ribose (cOMe). The functions of cOMe in animals, however, remain largely unknown. Here we show that the two cap methyltransferases (CMTr1 and CMT... Read More about CMTr cap-adjacent 2′-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses.

Two zinc finger proteins with functions in m6A writing interact with HAKAI (2022)
Journal Article
Zhang, M., Bodi, Z., Mackinnon, K., Zhong, S., Archer, N., Mongan, N. P., …Fray, R. G. (2022). Two zinc finger proteins with functions in m6A writing interact with HAKAI. Nature Communications, 13(1), Article 1127. https://doi.org/10.1038/s41467-022-28753-3

The methyltransferase complex (m6A writer), which catalyzes the deposition of N6-methyladenosine (m6A) in mRNAs, is highly conserved across most eukaryotic organisms, but its components and interactions between them are still far from fully understoo... Read More about Two zinc finger proteins with functions in m6A writing interact with HAKAI.

Modifying the m6A brain methylome by ALKBH5-mediated demethylation: a new contender for synaptic tagging (2021)
Journal Article
Martinez De La Cruz, B., Markus, R., Malla, S., Haig, M. I., Gell, C., Sang, F., …Knight, H. M. (2021). Modifying the m6A brain methylome by ALKBH5-mediated demethylation: a new contender for synaptic tagging. Molecular Psychiatry, 26(12), 7141-7153. https://doi.org/10.1038/s41380-021-01282-z

Synaptic plasticity processes, which underlie learning and memory formation, require RNA to be translated local to synapses. The synaptic tagging hypothesis has previously been proposed to explain how mRNAs are available at specific activated synapse... Read More about Modifying the m6A brain methylome by ALKBH5-mediated demethylation: a new contender for synaptic tagging.

mRNA adenosine methylase (MTA) deposits m6A on pri-miRNAs to modulate miRNA biogenesis in Arabidopsis thaliana (2020)
Journal Article
Bhat, S. S., Bielewicz, D., Gulanicz, T., Bodi, Z., Yu, X., Anderson, S. J., …Szweykowska-Kulinska, Z. (2020). mRNA adenosine methylase (MTA) deposits m6A on pri-miRNAs to modulate miRNA biogenesis in Arabidopsis thaliana. Proceedings of the National Academy of Sciences, 117(35), 21785-21795. https://doi.org/10.1073/pnas.2003733117

Copyright © 2020 the Author(s). Published by PNAS. In Arabidopsis thaliana, the METTL3 homolog, mRNA adenosine methylase (MTA) introduces N6-methyladenosine (m6A) into various coding and noncoding RNAs of the plant transcriptome. Here, we show that a... Read More about mRNA adenosine methylase (MTA) deposits m6A on pri-miRNAs to modulate miRNA biogenesis in Arabidopsis thaliana.

Characterization of CRISPR mutants targeting genes modulating pectin degradation in ripening tomato (2018)
Journal Article
Wang, D., Samsulrizal, N., Yan, C., Allcock, N. S., Craigon, J., Blanco-Ulate, B., …Seymour, G. B. (2019). Characterization of CRISPR mutants targeting genes modulating pectin degradation in ripening tomato. Plant Physiology, 179(2), 544-557. https://doi.org/10.1104/pp.18.01187

Tomato (Solanum lycopersicum) is a globally important crop with an economic value in the tens of billions of dollars, and a significant supplier of essential vitamins, minerals and phytochemicals in the human diet. Shelf life is a key quality trait r... Read More about Characterization of CRISPR mutants targeting genes modulating pectin degradation in ripening tomato.

N6-methyladenosine inhibits local ribonucleolytic cleavage to stabilise mRNAs in Arabidopsis (2018)
Journal Article
Anderson, S. J., Kramer, M. C., Gosai, S. J., Liu, X., Vandivier, L. E., Nelson, A. D., …Gregory, B. D. (2018). N6-methyladenosine inhibits local ribonucleolytic cleavage to stabilise mRNAs in Arabidopsis. Cell Reports, 25(5), 1146-1157. https://doi.org/10.1016/j.celrep.2018.10.020

N6-methyladenosine (m6A) is a dynamic, reversible, covalently modified ribonucleotide that occurs predominantly toward 30 ends of eukaryotic mRNAs and is essential for their proper function and regulation. In Arabidopsis thaliana, many RNAs contain a... Read More about N6-methyladenosine inhibits local ribonucleolytic cleavage to stabilise mRNAs in Arabidopsis.

Characterization of volatile aroma compounds after in-vial cooking of foxtail millet porridge with gas chromatography-mass spectrometry (2018)
Journal Article
Zhang, Y., Yang, N., Fray, R. G., Fisk, I., Liu, C., Li, H., & Han, Y. (in press). Characterization of volatile aroma compounds after in-vial cooking of foxtail millet porridge with gas chromatography-mass spectrometry. Journal of Cereal Science, 82, https://doi.org/10.1016/j.jcs.2018.05.003

Foxtail millet has become popular over recent years for its nutritional value and ecological functions. The aroma of foxtail millet is not well characterized, which is critical for its eating quality and understanding the biochemistry and genetics of... Read More about Characterization of volatile aroma compounds after in-vial cooking of foxtail millet porridge with gas chromatography-mass spectrometry.

Identification of factors required for m6A mRNA methylation in Arabidopsis reveals a role for the conserved E3 ubiquitin ligase HAKAI (2017)
Journal Article
Růžička, K., Zhang, M., Campilho, A., Bodi, Z., Kashif, M., Saleh, M., …Fray, R. G. (2017). Identification of factors required for m6A mRNA methylation in Arabidopsis reveals a role for the conserved E3 ubiquitin ligase HAKAI. New Phytologist, 215(1), 157-172. https://doi.org/10.1111/nph.14586

N6-adenosine methylation (m6A) of mRNA is an essential process in most eukaryotes, but its role and the status of factors accompanying this modification are still poorly understood. Using combined methods of genetics, proteomics and RNA biochemis... Read More about Identification of factors required for m6A mRNA methylation in Arabidopsis reveals a role for the conserved E3 ubiquitin ligase HAKAI.

Exogenous N-acyl-homoserine lactones enhance the expression of flagella of Pseudomonas syringae and activate defence responses in plants (2016)
Journal Article
Cheng, F., Ma, A., Zhuang, G., & Fray, R. G. (2017). Exogenous N-acyl-homoserine lactones enhance the expression of flagella of Pseudomonas syringae and activate defence responses in plants. Molecular Plant Pathology, 19(1), 104-115. https://doi.org/10.1111/mpp.12502

In order to cope with pathogens, plants have evolved sophisticated mechanisms to sense pathogenic attacks and to induce defence responses. The N-acyl-homoserine lactone (AHL)-mediated quorum sensing in bacteria regulates diverse physiological process... Read More about Exogenous N-acyl-homoserine lactones enhance the expression of flagella of Pseudomonas syringae and activate defence responses in plants.

m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination (2016)
Journal Article
Haussmann, I. U., Bodi, Z., Sanchez-Moran, E., Mongan, N. P., Archer, N., Fray, R. G., & Soller, M. (2016). m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature, 540(7632), 301-304. https://doi.org/10.1038/nature20577

N6-methyladenosine (m6A) is the most common internal modification of eukaryotic messenger RNA (mRNA) and is decoded by YTH domain proteins1, 2, 3, 4, 5, 6, 7. The mammalian mRNA m6A methylosome is a complex of nuclear proteins that includes METTL3 (m... Read More about m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination.

The effect of adenosine monophosphate deaminase overexpression on the accumulation of umami-related metabolites in tomatoes (2016)
Journal Article
Chew, B. L., Fisk, I. D., Fray, R., Tucker, G. A., Bodi, Z., Ferguson, A., …Seymour, G. B. (in press). The effect of adenosine monophosphate deaminase overexpression on the accumulation of umami-related metabolites in tomatoes. Plant Cell Reports, 36(1), https://doi.org/10.1007/s00299-016-2058-z

Taste is perceived as one of a combination of five sensations, sweet, sour, bitter, salty, and umami. The umami taste is best known as a savoury sensation and plays a central role in food flavour, palatability, and eating satisfaction. Umami flavour... Read More about The effect of adenosine monophosphate deaminase overexpression on the accumulation of umami-related metabolites in tomatoes.

Genetic improvement of tomato by targeted control of fruit softening (2016)
Journal Article
Uluisik, S., Chapman, N. H., Smith, R., Poole, M., Adams, G., Gillis, R. B., …Seymour, G. B. (2016). Genetic improvement of tomato by targeted control of fruit softening. Nature Biotechnology, 34, 950-952. https://doi.org/10.1038/nbt.3602

Controlling the rate of softening to extend shelf life was a key target for researchers engineering genetically modified (GM) tomatoes in the 1990s, but only modest improvements were achieved. Hybrids grown nowadays contain 'non-ripening mutations' t... Read More about Genetic improvement of tomato by targeted control of fruit softening.

Accessing low-oxidation state taxanes: is taxadiene-4(5)-epoxide on the taxol biosynthetic pathway? (2016)
Journal Article
Barton, N. A., Marsh, B. J., Lewis, W., Narraidoo, N., Seymour, G. B., Fray, R. G., & Hayes, C. J. (in press). Accessing low-oxidation state taxanes: is taxadiene-4(5)-epoxide on the taxol biosynthetic pathway?. Chemical Science, 7(5), https://doi.org/10.1039/c5sc03463a

We have shown for the first time that taxadiene (3) can be epoxidised in a regio- and diastereoselective manner to provide taxadiene-4(5)-epoxide (12) as a single diastereoisomer, and that this epoxide can be rearranged to give taxa-4(20),11(12)-dien... Read More about Accessing low-oxidation state taxanes: is taxadiene-4(5)-epoxide on the taxol biosynthetic pathway?.

Yeast m6A Methylated mRNAs Are Enriched on Translating Ribosomes during Meiosis, and under Rapamycin Treatment (2015)
Journal Article
May, S. T., Bodi, Z., Bottley, A., Archer, N., May, S., & Fray, R. G. (2015). Yeast m6A Methylated mRNAs Are Enriched on Translating Ribosomes during Meiosis, and under Rapamycin Treatment. PLoS ONE, 10(7), Article e0132090. https://doi.org/10.1371/journal.pone.0132090

Interest in mRNA methylation has exploded in recent years. The sudden interest in a 40 year old discovery was due in part to the finding of FTO’s (Fat Mass Obesity) N6-methyladenosine (m6 A) deaminase activity, thus suggesting a link between obesity-... Read More about Yeast m6A Methylated mRNAs Are Enriched on Translating Ribosomes during Meiosis, and under Rapamycin Treatment.

Adenosine methylation in Arabidopsis mRNA is associated with the 3? end and reduced levels cause developmental defects (2012)
Journal Article
Bodi, Z., Zhong, S., Mehra, S., Song, J., Graham, N., Li, H., …Fray, R. G. (2012). Adenosine methylation in Arabidopsis mRNA is associated with the 3′ end and reduced levels cause developmental defects. Frontiers in Plant Science, 3(48), Article 48. https://doi.org/10.3389/fpls.2012.00048

We previously showed that the N6-methyladenosine (m6A) mRNA methylase is essential during Arabidopsis thaliana embryonic development. We also demonstrated that this modification is present at varying levels in all mature tissues. However, the require... Read More about Adenosine methylation in Arabidopsis mRNA is associated with the 3? end and reduced levels cause developmental defects.