Functional Consequences Of The Plant Epitranscriptome

Award Number
Status / Stage
1 April 2019 -
31 March 2023
Duration (calculated)
03 years 11 months
Funding Amount
Funder/Grant study page
Contracted Centre
University of Nottingham
Principal Investigator
Professor Rupert Fray
PI Contact
WHO Catergories
Understanding Underlying Disease
Disease Type
Dementia (Unspecified)

CPEC Review Info
Reference ID708
ResearcherReside Team


Award NumberBB/S006478/1
Status / StageCompleted
Start Date20190401
End Date20230331
Duration (calculated) 03 years 11 months
Funder/Grant study pageBBSRC UKRI
Contracted CentreUniversity of Nottingham
Funding Amount£507,962.00


Eukaryotic mRNAs can be modified by the methylation of adenosine (m6A) and there are writers, readers and erasers of this epitranscriptome mark. Genes encoding the protein complex that “writes” the methylation, as well as some of the proteins that “read” m6A, have remained conserved since the last common ancestor of plants and metazoans nearly 1.5 billion years ago. m6A is essential for mammals and plants and null mutants die early in embryogenesis. However, using a range of genetic approaches, we have created a set of hypomorphic m6A writer proteins in which m6A levels are reduced by 90%. Methylation of mRNA has been shown to regulate gene expression at multiple levels including alternative splicing, alternative poladenylation, nuclear export, translation and decay. However, it is not clear which of these are more recently evolved “special cases” and which represent the ancient “core” function. Using a hypomorphic low m6A writer line in a genetic screen for suppressor mutations, we obtained more than 20 independent events that restored or partially restored normal plant growth. In some cases this was associated with m6A levels closer to wild type levels, but in other cases m6A levels remained low. Conceptually suppressors could result from altered writer, eraser or reader/interpreter functions, but only reader/interpreter mutations would be expected to suppress the low m6A phenotype without changing m6A levels. We have identified one suppressor mutant as encoding a ribosomal protein that is required for re-initiation after an upstream open reading frame (uORF) and we have shown that some uORF containing transcripts are mistranslated in low m6A plants. This proposal will identify and test the features and mechanisms by which m6A in 3′ sequences interacts with translation machinery to regulate expression of a specific mRNA subset. It will also characterise other suppressor mutants to identify regulators of reader, writer and eraser activity.


The aim of this project is to understand the way in which m6A regulates how some mRNAs are translated by ribosomes.