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in the genome.
In humans, reversers make up up to 38%
of the genome.
After the activation of the reverse locon, the mRNA, proteins, and cDNA generated by reverse transcription are often detrimental to the body, potentially causing neurodegenerative diseases and cancer; In addition, reverse locon transposation can cause DNA damage, genetic mutations, and genomic instability, not only leading to infertility but also driving the aging process [1-3].
Therefore, researchers often believe that reversing locon activation is harmful to living
organisms.
Although the body has evolved a very fine regulatory mechanism to silence the activity of the reversal locus, it is still possible that the reversal locon can be activated at a specific time of life development or in a specific tissue, and the reversal locon activation under this physiological condition may give the species new physiological functions
.
On November 18, 2022, Zhao Zhang's research group from the Department of Pharmacology and Cancer Biology at Duke University and Lu Wang's research group from the Institute of Biochemistry and Cell Biology (Center for Excellence in Molecular Cell Sciences) of the Chinese Academy of Sciences published an article in Nature Genetics Retrotransposon activation during Drosophila metamorphosis conditions adult antiviral responses
。 In this study, a tool for detecting reverse locon transposons in somatic cells was systematically established, and the jump events
of reverse locons were tracked in real time at the single-cell level.
This paper reveals the important role of the activation of reversal colons in specific developmental periods to initiate the host's innate immune system to resist the invasion of foreign viruses for a long time, and provides a new direction
for studying the potential physiological functions of reversal locons.
Zhang Zhao's group has long been working on the reversing of the jumping event of the reposon, while studying the regulation of transposons in the reproductive system (Lu Wang et al.
, Cell, 2018; Sunjing Moon et al.
, Dev Cell, 2018), also working to explore its function
in somatic cells.
In this study, the team first established a new system
for tracking transposon jumps in somatic cells using fruit flies as model animals.
Fruit flies are metamorphostically developing insects that go through the egg, larval, pupal and adult stages
.
During the pupal stage, fruit flies undergo metamorphosis, during which somatic tissue first degenerates and then rebuilds new somatic tissue
.
Interestingly, by tracking the activity and jumping events of MDG4 reversal locus during somatic tissue development in real time, this study found that MDG4 can specifically activate during the pupal phase and jump
only in newborn somatic cells.
The activation and transposition of the reversing locon at a specific time under this physiological condition suggests that MDG4 may have a specific function
in the development of fruit flies.
The innate immune system is a very critical natural barrier
against the invasion of foreign germs and thus the survival of the body.
The system is highly conserved in everything from yeast to plants and animals
.
Although the innate immune system does not produce an extremely efficient immune memory like the acquired immune system, studies have shown that the innate immune system shows better protection against the next bacterial infection after being infected by one germ [4].
In this study, it was shown that mdg4-specific activation in the pupal phase can activate the host's innate immune system by activating the antiviral function of the NF-κB protein Relish, thereby protecting adult fruit flies against exogenous virus invasion
.
Activation of mdg4 can promote the cleavage and nucleation effect of Relish, thereby enhancing the expression
of genes related to the innate immune system.
Interestingly, the study shows that only MDG4 activation in the pupal phase can activate the innate immune system to achieve long-term protection against foreign viruses
.
In conclusion, by tracking the jumping events of reversal colons during somatic cell development in real time, this study found that the host uses the activation of reversal locons at a specific time to activate the innate immune system to protect itself against the invasion
of foreign viruses.
Evolutionarily speaking, though, the arms race between the host and the reverser never stops
.
However, in the exercise of certain physiological functions, the host successfully achieved "enemy for us"
for the reverse seater.
Under physiological conditions, the activation of the reversal locus not only does not have a harmful effect on the host, but will help the host to perform a specific function
.
This phenomenon is not only found in fruit flies, and studies have found that there is also a specific period of reversal locon activation during human embryonic development - 8 cells to blastocysts - [5]; The activation and function of this specific period of reversal of the locus may be evolutionarily conserved and deserves our in-depth study
.
And transposon research will surely be able to bring us more new "surprises"
in the near future.
In this study, Dr.
Wang Lu and Lauren Tracy of Zhang Zhao's group were joint first authors (Dr.
Wang Lu was also the joint corresponding author).
This research was strongly supported
by Dr.
Weijia Su, Dr.
Axe Yang of the Zhang Zhao Group, Feng Yu of the Lu Wang Group, and Dr.
Neal Silverman of the University of Massachusetts Medical School.
It is reported that Zhang Zhao's laboratory (ZZ-Lab) recently discovered that the reverse locon produces a large amount of circular DNA during jumping (Fu Yang et al.
, bioRxiv, 2022), and the laboratory is now working to study the role of transposons and circular DNA in physiological and disease processes such as cancer, in order to provide new ideas and targets
for cancer research 。 Lu Wang's laboratory (established in May 2021) is actively exploring the new physiological functions of reversal colons and their regulatory networks
that are silenced during somatic development.
Both research groups are committed to the cultivation of team members, and we sincerely invite sincere people to join us for cooperation!
Original link: https://doi.
org/10.
1038/s41588-022-01214-9
Platemaker: Eleven
References
1.
H.
H.
Kazazian, Jr.
, J.
V.
Moran, Mobile DNA in Health and Disease.
N Engl J Med 377, 361-370 (2017).
2.
V.
Gorbunova et al.
, The role of retrotransposable elements in ageing and age-associated diseases.
Nature 596, 43-53 (2021).
3.
K.
H.
Burns, Transposable elements in cancer.
Nat Rev Cancer 17, 415-424 (2017).
4.
J.
Quintin, S.
C.
Cheng, J.
W.
van der Meer, M.
G.
Netea, Innate immune memory: towards a better understanding of host defense mechanisms.
Curr Opin Immunol 29, 1-7 (2014).
5.
E.
J.
Grow et al.
, Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells.
Nature 522, 221-225 (2015).
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