mRNA epigenetics: Charaterization of a novel layer of gene regulation for essential brain functions


   School of Biosciences

   Applications accepted all year round  Funded PhD Project (Students Worldwide)

About the Project

For over 40 years we know about modified nucleotides in mRNA, but the functions for these essential modifications are largely elusive. Recent characterization of the FTO (fat mass and obesity associated) gene as a demethylase of N6-methyladenosine (m6A) indicates key roles for mRNA methylation in neuronal control of body weight (1-3). FTO is highly expressed in the brain and has also been associated with other neurological disorders such as depression, epilepsy and Alzheimers disease.

We use a Drosophila genetic model system to investigate the biological function of these modifications (3, 4, 5). Our aim is to identify which mRNAs are modified and where in these mRNAs modifications are localised. Furthermore, we aim to characterize the molecular machinery that places these modifications and the signalling pathways that regulate the dynamics of them. Last, we like to know the biological functions for these modifications.

For information about research in our laboratory, please visit:

http://www.sollerlab.org

Biological Sciences (4)

Funding Notes

For this BBSRC funded project please apply here:
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References

1: Anreiter I, Tian YW, Soller M. (2023) The cap epitranscriptome: Early directions to a complex life as mRNA. Bioessays. 45:e2200198
2: Dezi, V., Ivanov, C., Haussmann, I. U. and Soller, M. (2016) mRNA modifications and their role in development and disease. Biochem. Soc. Trans. 44: 1385-93.
3: Roignant, J.Y. and Soller, M. (2017) m6A in mRNA: An ancient mechanism to fine tune gene expression. TiG 33: 380-390.
4: Haussmann, I.U., Bodi, Z., Sanchez-Moran, E., Mongan, N., Archer, N., Fray, R., and Soller, M. (2016) m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature 540: 301.
5: Haussmann IU, Wu Y, Nallasivan MP, Archer N, Bodi Z, Hebenstreit D, Waddell S, Fray R, Soller M. (2022) CMTr cap-adjacent 2'-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses. Nat Commun. 13:1209.

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