Biological function molecular pathways and druggability of DNMT2/TRDMT1.

5-methylcytosine (mC) is among the most common epigenetic modification in DNA and RNA molecules, and plays an important role in the animal development and disease pathogenesis. Interestingly, unlike other mC DNA methyltransferases (DNMTs), DNMT2/TRDMT1 has the double-substrate specificity and adopts a DNMT-similar catalytic mechanism to methylate RNA. Moreover, it is widely involved in a variety of physiological regulatory processes, such as the gene expression, precise protein synthesis, immune response, and disease occurrence.

Determinants of DNMT2/TRDMT1 preference for substrates tRNA and DNA during the evolution.

RNA methyltransferase DNMT2/TRDMT1 is the most conserved member of the DNMT family from bacteria to plants and mammals. In previous studies, we found some determinants for tRNA recognition of DNMT2/TRDMT1, but the preference mechanism of this enzyme for substrates tRNA and DNA remains to be explored. In the present study, CFT-containing target recognition domain (TRD) and target recognition extension domain (TRED) in DNMT2/TRDMT1 play a crucial role in the substrate DNA and RNA selection during the evolution.

Restricted tRNA methylation by intermolecular disulfide bonds in DNMT2/TRDMT1.

Reportedly, DNMT2/TRDMT1 mainly methylates tRNAs at C38 and prevents them from the cleavage under stress. It also plays an essential role in the survival and physiological homeostasis of organisms. Nevertheless, DNMT2/TRDMT1 exhibits much weaker tRNA methylation activity in vitro than other tRNA methyltransferases, TrmD and Trm5.

New substrates and determinants for tRNA recognition of RNA methyltransferase DNMT2/TRDMT1.

Methylation is a common post-transcriptional modification of tRNAs, particularly in the anticodon loop region. The cytosine 38 (C38) in tRNAs, such as tRNA, tRNA, tRNA, and tRNA, can be methylated by human DNMT2/TRDMT1 and some homologs found in bacteria, plants, and animals. However, the substrate properties and recognition mechanism of DNMT2/TRDMT1 remain to be explored.

NOX1 down-regulation attenuated the autophagy and oxidative damage in pig intestinal epithelial cell following transcriptome analysis of transport stress.

The previous study indicated that transport stress resulted in oxidative damage and autophagy/mitophagy elevation, companied by NOX1 over- expression in the jejunal tissues of pigs. However, the transportation-related gene expression profile and NOX1 function in intestine remain to be explicated. In the current study, differentially expressed genes involved in PI3K-Akt and NF-κB pathways, oxidative stress and autophagy process have been identified in pig jejunal tissues after transcriptome analysis following transportation.