Hydroxymethylcytosine (5hmC) is a modification that occurs in DNA and RNA and is mediated by Tet methyldioxygenases. Although the biological roles and functions of DNA methylation have been characterized, less is known about the effects of RNA 5hmC modifications. To address this, Delatte et al. used Drosophila as a system because they do not contain DNA 5hmC modifications and express a single functional Tet gene (dTet). Dot blot analysis of Drosophila S2 cell extracts using a 5hmC antibody revealed that polyadenylated RNAs were highly modified by 5hmC. On this basis, the authors reasoned that 5hmC modification might regulate translation. Sucrose-gradient fractionation of S2 cell extracts followed by dot blotting showed that mRNAs associated with polysomes had a high level of 5hmC content, while in vitro translation analysis of hydroxymethylated RNA templates indicated that 5hmC-modified RNA promoted translation. To determine whether these effects had any biological significance, Delatte et al. examined 5hmC and dTet levels during Drosophila embryogenesis and detected high expression of both in the larval brain. Consistent with the expression patterns, dTet mutant larvae, which expressed lower levels of 5hmC, had smaller brain size and decreased neuroblasts. Although these findings reveal new insights regarding 5hmC RNA modifications, further studies are needed to determine whether the 5hmC-mediated regulation of translation is related to the fly brain defects.