2018/02/28

Epigenetic inheritance through non-coding RNAs

Sperm non-coding RNAs mediate transgenerational epigenetic inheritance of traits

https://www.whatisepigenetics.com/paternal-environmental-lifestyle-factors-influence-epigenetic-inheritance/

Excerpt: "There is strong evidence that suggests certain environmental or lifestyle factors may lead to increased risk of developing chronic diseases. These factors such as diet, behavior, stress, exposure to pollutants, and physical activity have been known to cause epigenetic changes which may be passed down from one generation to the next. It is believed that a father’s exposure to environmental factors can play a role in an offspring’s epigenetic patterns and health.

Recent evidence suggests that sperm epigenetic modifications can survive reprogramming following fertilization and be inherited by the embryo. Three types of epigenetic modifications that can be paternally inherited are DNA methylation, histone modifications and noncoding RNAs (ncRNAs).

DNA methylation is the process by which methyl groups are added to cytosine or adenine and inhibit transcription. DNA methylation patterns are erased and reestablished during gametogenesis and embryogenesis. These two points provide susceptible windows for environmental exposures to alter methylation patterns. Changes in DNA methylation can induce abnormalities in chromatin structure and gene expression.

Studies have shown that certain DNA methylation marks can survive genome-wide reprogramming and be inherited. For example, paternal pre-diabetes has been demonstrated to increase the susceptibility of diabetes in an offspring due to altered sperm DNA methylation patterns. A father’s exposure to phthalates has been shown to impact epigenetic marks on sperm DNA and can have an impact on a couples’ ability to have children. Even stressed fathers might epigenetically pass on high blood sugar to their kids.

Noncoding RNAs are RNA fragments, such as miRNA, siRNA, piRNA and IncRNA, which regulate gene expression levels at the transcriptional and post-transcriptional level. During the sperm maturation process, sperm cells are able to uptake novel miRNAs. For example, miR-34c, which is the most abundant sperm miRNA, has been shown to be necessary for early embryonic cell division. This provides a mechanism in which ncRNA may be inherited and can have an impact on embryonic development and offspring health. miRNA-375 which is associated with paternal stress has been linked to depressive behavior and compromised glucose metabolism in offspring.

Another study found that obese males exhibited abnormal expression of several miRNAs in their sperm. The miRNAs are believed to pass on insulin resistance to offspring, which can cause diabetes. These results demonstrate the potential impact the ncRNA can have on embryonic development and induced epigenetic inheritance."
 
My comment: Human sperm contains thousands of RNA transcripts. The number of different long non-coding RNAs is more than 25,000 and different microRNAs are also counted in several thousands. Non coding RNAs are essential in stem cell programming. After the fertilization, embryonic cells are stem cells, which means they are lacking information structures required for cellular differentiation. Traits and characteristics of the developing embryo are established by these non-coding RNA transcripts in a process called epigenetic reprogramming. They transmit necessary epigenetic markers for DNA methylation patterns, histone markers and chromatin folding. Several studies confirm this scientific fact:

http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004296
http://dev.biologists.org/content/143/4/635

These crucial non-coding RNA molecules refute the Darwinian tree of life. By comparing non-coding RNA transcripts, we can find huge differences between organisms. For example, the similarity between human/chimp lncRNA transcripts is only under 30%. The more we understand about cellular mechanisms and regulatory factors, the weaker is the position of the pseudoscientific theory of evolution.