Wang, Fei. The novel RNA methylcytosine hydroxylase Tet in Drosophila and its requirement in neurons and muscles. Retrieved from https://doi.org/doi:10.7282/T3VT1W8V
DescriptionThe TET (Ten-eleven translocation) 1, 2 and 3 proteins have been shown to function as DNA hydroxymethylases in vertebrates and their requirements have been documented extensively. We show that in Drosophila hydroxymethylcytosine preferentially marks polyadenylated RNAs and is deposited by Tet. Due to the lack of Cytosine methylation in DNA, Drosophila serves as an ideal model to study the biological function of 5hmrC. We maped the transcriptome-wide hydroxymethylation landscape, revealing hydroxymethylcytosine in the transcripts of many genes, notably in coding sequences, and identified consensus sites for hydroxymethylation. We found that RNA hydroxymethylation may favor mRNA translation. We show that Tet is essential for viability as Tet complete loss-of-function animals die at the late pupal stage. We also characterized the temporal and spatial expression and requirement of Tet throughout Drosophila development. Tet is highly expressed in neuronal tissues and at more moderate levels in somatic muscle precursors in embryos and larvae. Depletion of Tet in muscle precursors at early embryonic stages leads to defects in larval locomotion and late pupal lethality. Although Tet knock-down in neuronal tissue does not cause lethality, Tet is essential for neuronal function during development and affects locomotion in larvae and adults, as well as the circadian rhythm of adult flies. Further, we report the function of Tet in ovarian morphogenesis. Together, our findings provide basic insights into the biological function of 5hmrC, a modification that is likely also regulated by Tet proteins in other species, and may illuminate observed neuronal and muscle phenotypes observed in vertebrates.