Transposable Elements, Inflammation, and Neurological Disease

Saleh, Aurian; Macia, Ángela; Muotri, Alysson R.

doi:10.3389/fneur.2019.00894

Cited by 114 publications

(135 citation statements)

References 161 publications

(219 reference statements)

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“…They can self-replicate and insert into various locations inside genome. Dysregulation of TE may lead to various illnesses like in ammatory diseases (13). The only active member in TE is retrotransposon which can "copy and paste" themselves through RNA intermediate.…”

Section: Introductionmentioning

confidence: 99%

Exogenous coronavirus interacts with endogenous retrotransposon in human cells

Yin

Liu

et al. 2020

Preprint

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Abstract Background: There is an increased global outbreak of diseases caused by coronaviruses affecting respiratory tracts of birds and mammals. Recent particularly dangerous coronaviruses are MERS-CoV, SARS-CoV and SARS-CoV-2, causing respiratory illness and even failure of several organs. However, profound impact of coronavirus on host cells remains elusive. Results: Here, we go deep into transcriptome of MERS-CoV, SARS-CoV and SARS-CoV-2 infected human lung-derived cells, and observed that infection of these coronaviruses all induced increase of retrotransposon expression through upregulation of TET genes. Similar upregulation of retrotransposon was also observed in SARS-CoV-2 infected human intestinal organoids. Retrotransposon upregulation will lead to increased genome instability and more frequent readthrough from retrotransposon to dysregulate gene expression. People with higher basal level of retrotransposon like cancer patients and aged people will have increased risk of symptomatic infection. Additionally, we show evidence supporting long-term epigenetic inheritance of retrotransposon upregulation. We also observed significant amount of chimeric transcripts of retrotransposon and SARS-CoV-2 RNA for potential human genome invasion of viral fragments, with the front and the rear part of SARS-CoV-2 genome being easier to form chimeric RNA, and this may apply for other coronaviruses. Here we suggest that primers and probes for nucleic acid detection should be designed in the middle of virus genome to identify live virus with higher probability. Conclusions: In summary, we propose that infection of coronaviruses especially SARS-CoV-2 induce retrotransposon activation, formation of chimeric coronavirus-retrotransposon RNA, and elicits more severe symptoms in patients with underlying diseases. More attention may need to be paid to potential harm contributed by retrotransposon dysregulation in treatment of coronavirus-infected patients.

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Section: Introductionmentioning

confidence: 99%

Exogenous coronavirus interacts with endogenous retrotransposon in human cells

Yin

Liu

et al. 2020

Preprint

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“…Prominent in eccDNA hotspots in terms of repetitive elements is the presence of retrotransposable elements discussed to participate in the pathogenesis of several neurodegenerative disorders, including ALS and autoinflammatory diseases, as well as in the process of aging [150] ( Table 1). The coincidence of TE de-repression in the diseased and aging CNS with their abundance in the moiety of eccDNAs harbored throughout the genome argues for a putative disposition of the CNS environment for eccDNA-related gene regulatory influences, as discussed for the aging process.…”

Section: Role In Neurodegenerative Disordersmentioning

confidence: 99%

Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration

Ain

Schmeer

Wengerodt

et al. 2020

IJMS

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Still unresolved is the question of how a lifetime accumulation of somatic gene copy number alterations impact organ functionality and aging and age-related pathologies. Such an issue appears particularly relevant in the broadly post-mitotic central nervous system (CNS), where non-replicative neurons are restricted in DNA-repair choices and are prone to accumulate DNA damage, as they remain unreplaced over a lifetime. Both DNA injuries and consecutive DNA-repair strategies are processes that can evoke extrachromosomal circular DNA species, apparently from either part of the genome. Due to their capacity to amplify gene copies and related transcripts, the individual cellular load of extrachromosomal circular DNAs will contribute to a dynamic pool of additional coding and regulatory chromatin elements. Analogous to tumor tissues, where the mosaicism of circular DNAs plays a well-characterized role in oncogene plasticity and drug resistance, we suggest involvement of the “circulome” also in the CNS. Accordingly, we summarize current knowledge on the molecular biogenesis, homeostasis and gene regulatory impacts of circular extrachromosomal DNA and propose, in light of recent discoveries, a critical role in CNS aging and neurodegeneration. Future studies will elucidate the influence of individual extrachromosomal DNA species according to their sequence complexity and regional distribution or cell-type-specific abundance.

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“…Retrotransposon insertions may also mediate chromosomal rearrangements and alter the local epigenetic environment, among other effects. Furthermore, as discussed below, there is increasing evidence that, apart from insertion mutation, elevated L1 expression, especially of its reverse transcriptase (RT) and endonuclease activities, may initiate DNA damage or an immune response [11,12]. Such phenomena could lead to embryo damage.…”

Section: Introductionmentioning

confidence: 99%

A potential new mechanism for pregnancy loss: considering the role of LINE-1 retrotransposons in early spontaneous miscarriage

Lou

Goodier

Qiang

2020

Reprod Biol Endocrinol

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LINE1 retrotransposons are mobile DNA elements that copy and paste themselves into new sites in the genome. To ensure their evolutionary success, heritable new LINE-1 insertions accumulate in cells that can transmit genetic information to the next generation (i.e., germ cells and embryonic stem cells). It is our hypothesis that LINE1 retrotransposons, insertional mutagens that affect expression of genes, may be causal agents of early miscarriage in humans. The cell has evolved various defenses restricting retrotransposition-caused mutation, but these are occasionally relaxed in certain somatic cell types, including those of the early embryo. We predict that reduced suppression of L1s in germ cells or early-stage embryos may lead to excessive genome mutation by retrotransposon insertion, or to the induction of an inflammatory response or apoptosis due to increased expression of L1-derived nucleic acids and proteins, and so disrupt gene function important for embryogenesis. If correct, a novel threat to normal human development is revealed, and reverse transcriptase therapy could be one future strategy for controlling this cause of embryonic damage in patients with recurrent miscarriages.

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Transposable Elements, Inflammation, and Neurological Disease

Cited by 114 publications

References 161 publications

Exogenous coronavirus interacts with endogenous retrotransposon in human cells

Exogenous coronavirus interacts with endogenous retrotransposon in human cells

Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration

A potential new mechanism for pregnancy loss: considering the role of LINE-1 retrotransposons in early spontaneous miscarriage

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