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Review
. 2024 Oct 2;14(10):1250.
doi: 10.3390/biom14101250.

Evolution of Repetitive Elements, Their Roles in Homeostasis and Human Disease, and Potential Therapeutic Applications

Jeffrey Snowbarger  1 , Praveen Koganti  1 , Charles Spruck  1
Affiliations
Review

Evolution of Repetitive Elements, Their Roles in Homeostasis and Human Disease, and Potential Therapeutic Applications

Jeffrey Snowbarger et al. Biomolecules. .

Abstract

Repeating sequences of DNA, or repetitive elements (REs), are common features across both prokaryotic and eukaryotic genomes. Unlike many of their protein-coding counterparts, the functions of REs in host cells remained largely unknown and have often been overlooked. While there is still more to learn about their functions, REs are now recognized to play significant roles in both beneficial and pathological processes in their hosts at the cellular and organismal levels. Therefore, in this review, we discuss the various types of REs and review what is known about their evolution. In addition, we aim to classify general mechanisms by which REs promote processes that are variously beneficial and harmful to host cells/organisms. Finally, we address the emerging role of REs in cancer, aging, and neurological disorders and provide insights into how RE modulation could provide new therapeutic benefits for these specific conditions.

Keywords: co-option; epigenetic alteration; genomic instability; novel antigens; repetitive elements; transposable elements; viral mimicry.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 2
Figure 2
Roles of REs in beneficial and pathological processes. This figure describes the general methods by which RE activity in the genome can be either beneficial or harmful to the host cell and/or organism and represents what is discussed in Section 3.2 and Section 3.3. The dashed line separating the transposition and genomic instability categories signifies that transposition is also a form of genomic instability. SASP: senescence-associated secretory phenotype; RVLP: retrovirus-like particle. Created with BioRender.com (Accessed on 14 May 2024).
Figure 1
Figure 1
RE derepression leads to viral mimicry and inflammation through cytosolic nucleic acid sensing pathways. Loss of repressive epigenetic marks can derepress REs, leading to the production of cytosolic nucleic acids through retrotransposition intermediates or genomic stress (i.e., micronuclei or cytoplasmic chromatin fragments (CCFs)). Upon detection by pattern recognition receptors RIG-1, MDA5, and cGAS, downstream interferon and interferon-stimulated genes (ISGs) are expressed, leading to an inflammatory phenotype. RNA sensors activate MAVS, which oligomerizes on mitochondria, and cGAS activates STING through 2′3′ cGAMP, stimulating its translocation from the ER to the Golgi. Both pathways converge on TBK1/IKKs to phosphorylate IRF3/7 and NF-κB to induce transcription of interferons (IFNs) that, in an autocrine manner, initiate expression of ISGs. ISG expression can induce further cytokine and chemokine production, increased antigen processing, and NK cell ligand expression. This figure was inspired by and aims to expand on Figure 2 of [69] where the cytosolic dsRNA sensing pathway is explored. Other references for this figure include [70,71,72,73,74]. Created with BioRender.com (Accessed on 14 May 2024).
Figure 3
Figure 3
Potential therapeutic applications of RE modulation. This figure represents a non-exhaustive list of potential therapeutic avenues related to modulating RE expression. Information is presented in Section 5.1 and Section 5.2 of the text. Importantly, the top half of the figure represents potential cancer therapeutic strategies in which it is beneficial to induce RE activation. The bottom half represents aging and neurological diseases in which it is beneficial to repress RE activity. Created with BioRender.com (Accessed on 14 May 2024).
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References

    1. Avery O.T., MacLeod C.M., McCarty M. Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types. J. Exp. Med. 1944;79:137–158. doi: 10.1084/jem.79.2.137. - DOI - PMC - PubMed
    1. McClintock B. The Origin and Behavior of Mutable Loci in Maize. Proc. Natl. Acad. Sci. USA. 1950;36:344–355. doi: 10.1073/pnas.36.6.344. - DOI - PMC - PubMed
    1. Britten R.J., Kohne D.E. Repeated Sequences in DNA: Hundreds of Thousands of Copies of DNA Sequences Have Been Incorporated into the Genomes of Higher Organisms. Science. 1968;161:529–540. doi: 10.1126/science.161.3841.529. - DOI - PubMed
    1. Kit S. Equilibrium Sedimentation in Density Gradients of DNA Preparations from Animal Tissues. J. Mol. Biol. 1961;3:711–716. doi: 10.1016/S0022-2836(61)80075-2. - DOI - PubMed
    1. Smith D.R. Common Repeat Elements in the Mitochondrial and Plastid Genomes of Green Algae. Front. Genet. 2020;11:465. doi: 10.3389/fgene.2020.00465. - DOI - PMC - PubMed

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