tsRNAs are Novel Paternal Epigenetic Factors

06/12/2018 by Campion Fund

tsRNAs are novel paternal epigenetic factors that impact male reproductive health and effect the offspring of fathers.  Qi Chen, PhD of the University of Nevada, Reno, and colleagues have demonstrated that sperm transfer RNA-derived small RNAs (tsRNAs) are present in a mouse model in late spermatogenesis and in mature sperm.  Theses tsRNAs are concentrated in sperm heads and contribute to intergenerational inheritance. They are 30-34 nucleotides long and have the same 5’ ends but different 3’ ends.  When male mice are fed high fat diets their tsRNAs exhibit altered expression profiles.  Sperm tsRNAs from the high fat diet males injected into normal mouse zygotes produce metabolic disorders.  Expression of metabolic pathways in early embryos and F1 offspring were altered.  This mechanism is unrelated to the epigenetic mechanism of DNA methylation.  Furthermore, tsRNAs have been shown by Chen and colleagues to be distinct from piRNAs which are also small RNAs involved in epigenetic inheritance.  Interestingly, Dnmt2 – tRNSA methyl transferase- abolished sperm tsRNA transmission of high fat disorders in offspring. Thus, sperm can deliver paternal genetic information through RNA in addition to providing DNA.

Dr. Chen and colleagues speculate the tsRNA-derived small RNAs might be essential in a sperm RNA “coding signature” needed by paternal epigenetic memory.  They are now interested in studying this epigenetic mechanism in human sperm.  In addition, he plans to work with collaborators to determine the effects of air pollution, chemical toxins and endocrine disruptors on intergenerational inheritance mediated through tsRNAs.  It will be very interesting to see what they discover.  If indeed, toxins and pollutants are involved in epigenetic changes in humans the public health consequences are significant.

References: Peng H, Shi J, ……Chen Q,.. et al,  A novel class of tRNA-derived-small RNAs extremely enriched in mature mouse sperm. Cell Res. 2012, 22: 1609-1612

Chen Q, Yan M, Cao Z et al. Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science 2016. 6271: 397-400

Zhang Y, Zhang X, Sen J…….Chen Q.  Dnmt2 mediates intergenerational transmission of paternatal acquired metabolic disorders through sperm small non-conding RNA mechanisms

Nat Cell Biology 2018, 20:535-540

Phyllis C. Leppert, MD, PhD