A new paper adds another RNA modification to the list already published, but with exciting news for the epigenetics enthusiasts out there… the characterized modification is RNA 5-hydroxymethylcytosine (5hmrC), an important mark previously discovered on DNA.
The laboratory of François Fuks at ULB in Brussels decided to look deeper into the presence of 5hmC on RNA, which had been shown to exist in various domains of life. Specifically, they chose to look at it in Drosophila, which have very little or no DNA methylation.
After verifying via dot blot and RNase treatment that 5hmrC was present in Drosophila, they found that:
- 5hmrC was enriched in the polyadenylated fraction of the RNA loaded onto ribosomes, especially polysomes.
- When they knocked down the Tet gene of Drosophila (dTet) 5hmrC levels decreased.
- hMeRIP (5hmrC IP and then sequencing) showed that the modification was present mainly in the coding regions of developmental, embryogenesis and basic cellular process genes.
- dTet knock down reduced the expression of only some of the transcripts with 5hmrC, suggesting that Tet has other roles besides 5hmrC deposition.
- In rabbit reticulocytes in vitro, 5hmrC levels were positively correlated with transcript abundance.
By expressing GFP during embryogenesis under the control of the endogenous Tet promoter, the authors found that dTet was likely to be most strongly expressed in the larval brain. dTet-deficient flies overcame the larvae stage, albeit with smaller brains than their wild-type counterparts and abnormally organized neuroblasts, but died at the pupa stage.
This exciting finding will hopefully be one of many in this new field of epitranscriptomics. Check it out at Science, Jan 2016.