A lncRNA-like Role for LINE1s in Development

Honson, Drew D.; Macfarlan, Todd S.

doi:10.1016/j.devcel.2018.06.022

Cited by 28 publications

(20 citation statements)

References 10 publications

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“…More recently, using antisense oligonucleotides to deplete L1 transcripts, Percharde et al [126,127] presented evidence that LINE1 expression plays a role in mouse embryonic exit from the 2-cell stage by recruiting nucleolin and Kap1 to repress the master transcriptional regulator Dux and activate rRNA synthesis. Furthermore, Jachowicz et al [128] reported that LINE-1 activation after fertilization regulates global chromatin accessibility, and that artificial prolongation of L1 transcription in mouse embryos interferes with their development.…”

Section: A Possible Role For Misregulation Of Retrotransposon Expressmentioning

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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Section: A Possible Role For Misregulation Of Retrotransposon Expressmentioning

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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“…REs can serve as genes for long ncRNAs (Lu et al, 2014). L1s have a function similar to lncRNA in regulating the expression of genes necessary for self-renewal of stem cells and for preimplantation development (Honson, Macfarlan, 2018).…”

Section: The Relationship Of Transposable Elements With Non-coding Rnmentioning

confidence: 99%

“…Despite the lack of mitotic activity of mature neurons, the specific expression of TEs in them is important in controlling both interneuronal interactions and the structural and functional characteristics of neurons (Bailie et al, 2011;Richardson et al, 2014;Erwin et al, 2016). These properties may be due to processing from transcripts of transposons of specific long ncRNAs (Lu et al, 2014;Honson, Macfarlan, 2018) and microRNAs (Piriyapongsa et al, 2007;Yuan et al, 2010Yuan et al, , 2011Qin et al, 2015). Indeed, in experiments on laboratory animals, the enrichment of specific miRNAs in certain structures and regions of neurons was revealed.…”

Section: The Role Of Retroelements In Interactions Between Neuronsmentioning

confidence: 99%

Involvement of transposable elements in neurogenesis

Мустафин

Хуснутдинова

2020

Vestn. VOGiS

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The article is about the role of transposons in the regulation of functioning of neuronal stem cells and mature neurons of the human brain. Starting from the first division of the zygote, embryonic development is governed by regular activations of transposable elements, which are necessary for the sequential regulation of the expression of genes specific for each cell type. These processes include differentiation of neuronal stem cells, which requires the finest tuning of expression of neuron genes in various regions of the brain. Therefore, in the hippocampus, the center of human neurogenesis, the highest transposon activity has been identified, which causes somatic mosai cism of cells during the formation of specific brain structures. Similar data were obtained in studies on experimental animals. Mobile genetic elements are the most important sources of long non-coding RNAs that are coexpressed with important brain protein-coding genes. Significant activity of long non-coding RNA was detected in the hippocampus, which confirms the role of transposons in the regulation of brain function. MicroRNAs, many of which arise from transposon transcripts, also play an important role in regulating the differentiation of neuronal stem cells. Therefore, transposons, through their own processed transcripts, take an active part in the epigenetic regulation of differentiation of neurons. The global regulatory role of transposons in the human brain is due to the emergence of protein-coding genes in evolution by their exonization, duplication and domestication. These genes are involved in an epigenetic regulatory network with the participation of transposons, since they contain nucleotide sequences complementary to miRNA and long non-coding RNA formed from transposons. In the memory formation, the role of the exchange of virus-like mRNA with the help of the Arc protein of endogenous retroviruses HERV between neurons has been revealed. A possible mechanism for the implementation of this mechanism may be reverse transcription of mRNA and site-specific insertion into the genome with a regulatory effect on the genes involved in the memory.

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“…In plants, transposon‐derived long non‐coding RNAs (TE‐lncRNAs) appear to be involved in stress responses (Wang et al, ) and root development (Cho & Paszkowski, ). In mammals, a LINE1 ‐derived lncRNA acts as a nuclear scaffold to modulate the expression profiles of crucial genes involved in ESC self‐renewal and pre‐implantation embryo development (Honson & Macfarlan, ; Percharde et al, ). Similarly, another TE‐lncRNA (human pluripotency‐associated transcript 5, HPAT5), derived from the endogenous retrovirus HUERS‐P1 and an Alu element, promotes pluripotency in pre‐implantation embryo development by functioning as a molecular sponge for let‐7 microRNAs (Durruthy‐Durruthy et al, ; Izsvák, Wang, Singh, Mager, & Hurst, ).…”

Section: Transposable Elements As Drivers Of Genome Plasticitymentioning

confidence: 99%

Environmental change and the evolution of genomes: Transposable elements as translators of phenotypic plasticity into genotypic variability

Pimpinelli

Piacentini

2019

Functional Ecology

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Phenotypic plasticity is generally explained as the result of epigenetic mechanisms modifying gene expression in response to changing environmental conditions. However, the biology of transposable elements (TEs) suggests that such elements may also induce differential gene expression by affecting regulatory regions. We discuss the ecological and evolutionary relevance of epigenetic modifications versus transposon activity, taking into account that epigenetic modifications are generally reversible but that the modifications induced by TEs are stably inherited. We outline our perspective on the multiple roles played by environmental changes in the context of adaptive evolution. Environmental perturbations can induce phenotypic variations via epigenetic modulation of gene expression and promote, at the same time, genetic variability by triggering bursts of TE activity; finally, they select which genetic variations are most advantageous for survival. Within this context, the production of environmentally induced advantageous phenotypes by epigenetic mechanisms could represent an immediate process of adaptation followed by TE‐induced genotypic changes that make these phenotypic variants heritable through the germ line. This scenario could lead TEs to play different roles in the function of the time‐scale of ecological variation, such as those related to climatic change in the current context of global change. In conclusion, we propose that through TE activation, environmental changes can act as inducers of genetic variability, upon which they also act as selective forces, thus triggering rapid evolutionary processes. A free Plain Language Summary can be found within the Supporting Information of this article.

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A lncRNA-like Role for LINE1s in Development

Cited by 28 publications

References 10 publications

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

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

Involvement of transposable elements in neurogenesis

Environmental change and the evolution of genomes: Transposable elements as translators of phenotypic plasticity into genotypic variability

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