This episode is entitled RNA: birth to death and this can have two different meaning for people. 1) the role of RNA from the beginning of life until death (or even after!). 2) the meaning it has for most RNA biologists, which is the birth of an RNA molecule through the process of transcription that we have talked about before, all the way to its death through degradation. We will be talking about the former today, maybe at a later date we can touch on the latter.
Keep in mind that many of these subjects have been studied for decades so we are just going to be surfing the waves of a deep ocean of research. And we will be mostly focused on the life of mammals, but many of these processes are highly conserved, meaning they are the same in many forms of life from plants to insects to us.
The moment of life as we know begins when an egg from the mom (called an ovum) meets the winning sperm from the dad. This fusion results in the formation of a zygote (from the Greek word zygotos= to yoke/to join), which combines DNA from mom and dad and is basically each one of us at a single cell stage. The interesting thing to note here on an RNA standpoint, is that the zygote is transcriptionally inactive meaning it is not producing any RNA on its own, it relies completely on maternal RNA transcripts and proteins that were stored in the egg before fertilization. Even after transcription begins in the zygote there is still a heavy reliance on the mother’s RNA, without which the zygote won’t get very far. For example, the zona pellucida, which means the “transparent zone” in Latin, is a layer that covers the egg and early embryo and is created and maintained by maternal RNA and proteins. This layer allows sperm to bind to the egg but then when one sperm gets to the finish line, the zona pellucida switches jobs and prevents any other sperm from getting inside the egg. Once the egg is fertilized, paternal DNA is unpacked and the zygote starts going through this process called maternal to zygotic transition where the maternal RNA starts getting degraded and the zygote starts making its own RNA resulting in a brand new person.
During puberty, there is another huge overhaul to our bodies’ transcriptional profile and this time those changes are caused by different hormones released and circulated in the body. There are sex-based differences for males and females, but we are just going to talk about the aspects of this process that are shared. This process begins in the brain and causes a cascade of different hormones to be released, ending (or really beginning) with the production of estradiol (a class of estrogen) and testosterone in females and males. These hormones cause widespread changes to many tissues and organs including the bones, muscle, fat, skin, hair, vocal cords, reproductive organs, and brain. And these changes occur because each hormone can bind to the cells of these tissues and create changes in the type and amount of RNA generated from various genes.
Moving further along the timeline, RNA biology is also key during the process of ageing. As we age the RNA profiles in our tissues start to look different than they used to. Studies have shown that some tissues like the eye can show significant change over the course of one’s lifetime, but others like the liver remain relatively constant. It has also been demonstrated that RNA profiles in young tissues are very tightly controlled but as we age, the profiles become more relaxed. As we age the ability of mRNA to be translated into protein also becomes less efficient. Each of these examples may seem small by themselves, and in reality, only result in tiny changes, but together the add up to an ageing body[PP3] . Scientists are actively researching how to modify many of these areas to slow down or reverse the ageing process.
Now let’s talk about death. While that might be the end of the road for us, it may surprise you that it is not the end for our RNA. Of course, the vast majority of RNA is reducing after death because it is being degraded but hundreds of mRNA transcripts are actually increasing in abundance in the minutes, hours and days after death. These transcripts regulate a few different areas of biology. 1) Stress-related: these are genes that try to balance stresses put on the body, and given that death can be quite stressful, we can see changes in genes that turn on in response to low oxygen levels, to fix protein processing that gets perturbed upon death, and to initiate protein degradation and cell death. Genes involving immune responses against viruses and bacteria are also turned on. Surprisingly, many genes that regulate embryonic development are also turned on. Research suggests that it’s because the conditions in the body after death somewhat resemble the conditions in an embryo, so death has restarted processes that have been silenced since embryogenesis.
As a last note, while the results presented happened up to 48h postmortem, researchers have found that many cells in our body become dormant, but do not die for days after death. Skeletal muscle stem cells from mice can return to regenerating 17 days after death, another cell type called fibroblasts can be grown in the lab 160 days after death. Takes the meaning of “life after death” to a very plausible dimension.
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