Figure 7.

Roles of tRFs in metabolic disorders and β-cell dysfunction. (A) Paternal high fat diet (HFD) increases the abundance of tiRNA-5s that are packaged inside epididymis-derived exosomes (epididymosomes). Epididymosomes fuse with the sperm and transfer these fragments. When normal zygotes are fertilized with HFD sperm or microinjected with tRFs isolated from HFD sperm, expression of metabolic genes in eight-cell and blastocyst-stage embryos is drastically altered. The resulting offspring exhibit abnormal metabolism at adulthood, including glucose intolerance and alterations in pancreatic islet transcriptome. A similar metabolic function of tRFs is observed upon a paternal low protein diet. (B) TRMT10A deficiency is associated with hypomethylation of guanosine residues at position 9 of certain tRNAs. Hypomethylated tRNAs are transported to the cytoplasm and fragmented. tRF-5s generated from such fragmentations lead to β-cell apoptosis.