Postmortem gene expression: new data
When our body dies, the genes continue to work
Maria Perepechaeva, "First-hand Science"
Does the life of our body end with death? The answer to this question is not as unambiguous as it seems – at least in relation to genes. The fact that in human blood and liver cells, some genes continue to work for some time after death has been known for a long time. And in recent years, in postmortem studies on laboratory animals, it has been found that in a dead body, contrary to expectations, the work of certain genes does not just slow down, but even activates.
Back in 2016, an international team of scientists led by P. A. Noble from Washington State University conducted a post–mortem assessment of the activity of more than a thousand genes using the example of a house mouse and the famous aquarium fish danio rerio - popular and well-studied model objects in genetics and developmental biology. Mice were observed for two days after the death of the animal, fish – for four days.
To the great surprise of the researchers, almost half of all the studied genes after the death of animals increased their activity, estimated by the number of transcripts – RNA molecules "read" from the sequence of gene DNA, which serve as matrices for protein synthesis. Most of them became active within the first half hour after death, some – after a day, while in danio rerio some genes remained active during all the days of postmortem observation!
The "record holders" included genes involved in the activation of the immune system and the inflammatory process, involved in the process of "cell suicide" – apoptosis, etc. The behavior of this group of "rapid response" genes can to some extent be considered an attempt to "resuscitate" the deceased organism. But this cannot explain, for example, the activation of other genes – those that "work" only at the earliest, embryonic stage of development. The most important is the fact of activation after death of so-called oncogenes, because of which, apparently, people who have transplanted organs from recently deceased donors are more likely to get cancer.
A natural continuation of this work was the search for regulatory mechanisms underlying the postmortem activation of genes. For this purpose, a bioinformatic analysis of control and postmortem pools of matrix RNAs was carried out, which allowed comparing the number of sites where regulatory molecules bind (Noble & Pozhitkov, Distinct sequence patterns in the active postmortem transcriptome //bioRxiv, 2018).
As is known, mRNA can be regulated at different stages: either directly in the process of transcription (reading from DNA), or at the stage of the "finished" molecule. Such post-transcriptional regulation is more beneficial energetically, therefore, under stressful conditions, up to 90% of mRNA is regulated in this way. It is carried out with the help of special RNA-binding proteins, which, when attached to mRNA, protect it from degradation. Conversely, a variety of non-coding microRNAs can block mRNA activity and, accordingly, protein synthesis. In turn, some RNAs can act as a molecular "sponge", blocking regulatory microRNAs themselves.
There are many options here, and the researchers assumed that in this case they would be able to detect a single mechanism of such post-transcriptional regulation. However, they did not receive an unambiguous answer. And although different groups of animals did differ in the regulatory sites of molecules from the mRNA pool, a large variety of these differences rather testified in favor of the existence of several regulatory pathways. Scientists will continue their research, but for us the most important thing is not even these mechanisms themselves, but the fact that they can be activated not only after death, but also during life – in a situation of super-strong cellular stress. For example, with oncological diseases or prolonged fasting. And the results of such unconventional work may in the future be useful for practical medicine. At least now they allow us to develop approaches to the assessment of donor material, as well as the exact determination of the time of death of a person during a forensic examination.
In any case, by observing the postmortem work of genes, we will be able to learn more about both death and life, the boundary between which turned out to be more blurred than we expected.
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