Factors Regulating the Activity of LINE1 Retrotransposons

Abstract

LINE-1 (L1) is a class of autonomous mobile genetic elements that form somatic mosaicisms in various tissues of the organism. The activity of L1 retrotransposons is strictly controlled by many factors in somatic and germ cells at all stages of ontogenesis. Alteration of L1 activity was noted in a number of diseases: in neuropsychiatric and autoimmune diseases, as well as in various forms of cancer. Altered activity of L1 retrotransposons for some pathologies is associated with epigenetic changes and defects in the genes involved in their repression. This review discusses the molecular genetic mechanisms of the retrotransposition and regulation of the activity of L1 elements. The contribution of various factors controlling the expression and distribution of L1 elements in the genome occurs at all stages of the retrotransposition. The regulation of L1 elements at the transcriptional, post-transcriptional and integration into the genome stages is described in detail. Finally, this review also focuses on the evolutionary aspects of L1 accumulation and their interplay with the host regulation system.

Potential health risks of mRNA-based vaccine therapy: A hypothesis

“…However, prior to implantation, the inner cell mass and trophectoderm cells show de novo endogenous LINE-1 insertions [77] , and in vitro studies with embryonic stem cells and pluripotent stem cells have described endogenous LINE-1 transcription and translation which lead to retrotransposition [78] . This is because during the initial stages of embryogenesis, the cellular milieu supports active retrotransposition of LINE-1 [79] , and embryonic somatic cells down-regulate the molecular restrictions of LINE-1 retrotransposition, most likely because LINE-1 activity plays a key role in generating somatic mosaicism [80] . Interestingly, in post-natal organisms, some cell types, including neurons and glial cells, have fewer restrictions on LINE-1 activity leading to somatic genome variation in the nervous system [70] , [81] , which contributes to neurogenesis [82] but also to neuropsychiatric diseases when LINE-1 activity is abnormally high [83] .…”

Transposable Elements and Human Diseases: Mechanisms and Implication in the Response to Environmental Pollutants

“…Indeed, the regulation of LINE-1 expression and activity is rather complex and includes, but is not limited to, epigenetic controls and interaction with several DNA repair proteins that act as inhibitors of LINE-1 integration in the genome (reviewed in [ 35 ]). For example, core proteins of the nucleotide excision repair (NER) pathway, XPD and XPA, the lesion binding protein, XPC, and the endonuclease complex ERCC1-XPF, limits LINE-1 retrotransposition.…”

Involvement of retroelements in the autoimmune response in humans

“…L1-enriched nucleic acids could induce the production of type I interferon (IFN), resulting in complex series of events which cause systemic autoimmune diseases. Type I IFN is crucial for the innate defense mechanism in mammals against viruses [2,[14][15][16]]. An autoimmune response can be induced by the retroelements in various ways such as insertional mutagenesis, sensing of retroelement RNA/cDNA, or error-prone reverse transcription of retroelement messenger RNA (mRNA), resulting in mimotopes [17].…”