Researchers often use a nematode worm called Caenorhabditis elegans (C. elegans) to study human genetics because at the molecular level, we have a lot in common with these organisms. Scientists used a C. elegans models to show that when fathers are exposed to stress, toxins, or an unhealthy diet, it can lead to behavioral issues or metabolic disorders in their offspring. Now, researchers have learned more about a molecular mechanism that may underlie this phenomenon, without altering the sequence of DNA. This research has indicated that molecules known as small RNAs can originate from sperm, and be passed down to influence the earliest stages of development in offspring. The findings have been published in Cell Reports.
In this work, the scientists zeroed in on one small RNA in particular, known as tRFValCAC. As sperm matured in the male reproductive tract, tRFValCAC become highly concentrated in that sperm. This study showed that cells in the epididymis, which is where sperm complete their development, use little sacs called extracellular vesicles (EVs) to transmit tRFValCAC into sperm.
One protein in particular was shown to bind to tRFValCAC to control how much of it ends up going into EVs, and eventually, into sperm. When the investigators lowered the levels of this protein, there was less tRFValCAC in sperm.
"This has opened new avenues of investigation for us. We will next investigate how this protein is regulated and which other proteins are involved in packaging small RNAs in sperm,” said senior study author Upasna Sharma, an assistant professor at the University of California, Santa Cruz.
During fertilization, sperm releases tRFValCAC into the egg. When the activity of tRFValCAC was blocked, the regulation of gene activity in embryos was disrupted and cell division was impaired. The researchers found that tRFValCAC normally works to control gene activity in the early embryo, particularly genes that are related to chromosomal organization, cell division, and RNA processing.
The small RNA from sperm seems to control the pace of some processes during embryonic development. The environment may be able to cause changes in sperm RNAs, which can ultimately affect early development and eventually an individual’s risk of certain diseases, without any underlying mutations in DNA.
This research may help us understand how epigenetic changes, which alter gene activity but not the genetic sequence, can influence developmental processes and the risk of developing a disease during a lifetime.
Sources: University of California - Santa Cruz, Cell Reports
