Transposable Elements, Inflammation, and Neurological Disease

Overview

Journal Front Neurol

Specialty Neurology

Date 2019 Sep 5

PMID 31481926

Citations 65

Authors

Aurian Saleh

Angela Macia

Alysson R Muotri

Affiliations

Soon will be listed here.

Abstract

Transposable Elements (TE) are mobile DNA elements that can replicate and insert themselves into different locations within the host genome. Their propensity to self-propagate has a myriad of consequences and yet their biological significance is not well-understood. Indeed, retrotransposons have evaded evolutionary attempts at repression and may contribute to somatic mosaicism. Retrotransposons are emerging as potent regulatory elements within the human genome. In the diseased state, there is mounting evidence that endogenous retroelements play a role in etiopathogenesis of inflammatory diseases, with a disposition for both autoimmune and neurological disorders. We postulate that active mobile genetic elements contribute more to human disease pathogenesis than previously thought.

Citing Articles

The Role of Epigenetic Mechanisms in the Development of PM-Induced Cognitive Impairment.

Jiang L, Shao M, Song C, Zhou L, Nie W, Yu H Toxics. 2025; 13(2).

PMID: 39997934 PMC: 11861554. DOI: 10.3390/toxics13020119.

p53-mediated regulation of LINE1 retrotransposon-derived R-loops.

Paul P, Kumar A, Parida A, De A, Bhadke G, Khatua S J Biol Chem. 2025; 301(3):108200.

PMID: 39828096 PMC: 11903798. DOI: 10.1016/j.jbc.2025.108200.

HiTE: a fast and accurate dynamic boundary adjustment approach for full-length transposable element detection and annotation.

Hu K, Ni P, Xu M, Zou Y, Chang J, Gao X Nat Commun. 2024; 15(1):5573.

PMID: 38956036 PMC: 11219922. DOI: 10.1038/s41467-024-49912-8.

Retrotransposons in embryogenesis and neurodevelopment.

Talley M, Longworth M Biochem Soc Trans. 2024; 52(3):1159-1171.

PMID: 38716891 PMC: 11346457. DOI: 10.1042/BST20230757.

Knockdown of PGBD5 inhibits the malignant progression of glioma through upregulation of the PPAR pathway.

Luo P, Yang J, Jian L, Dong J, Yin S, Luo C Int J Oncol. 2024; 64(5).

PMID: 38577941 PMC: 11015917. DOI: 10.3892/ijo.2024.5643.

References

Christensen T, Dissing Sorensen P, Riemann H, Hansen H, Munch M, Haahr S . Molecular characterization of HERV-H variants associated with multiple sclerosis. Acta Neurol Scand. 2000; 101(4):229-38. DOI: 10.1034/j.1600-0404.2000.101004229.x. View

Andrews W, Tuke P, Al-Chalabi A, Gaudin P, Ijaz S, Parton M . Detection of reverse transcriptase activity in the serum of patients with motor neurone disease. J Med Virol. 2000; 61(4):527-32. DOI: 10.1002/1096-9071(200008)61:4<527::aid-jmv17>3.0.co;2-a. View

Martin S, Bushman F . Nucleic acid chaperone activity of the ORF1 protein from the mouse LINE-1 retrotransposon. Mol Cell Biol. 2001; 21(2):467-75. PMC: 86601. DOI: 10.1128/MCB.21.2.467-475.2001. View

Lander E, Linton L, Birren B, Nusbaum C, Zody M, Baldwin J . Initial sequencing and analysis of the human genome. Nature. 2001; 409(6822):860-921. DOI: 10.1038/35057062. View

Speek M . Antisense promoter of human L1 retrotransposon drives transcription of adjacent cellular genes. Mol Cell Biol. 2001; 21(6):1973-85. PMC: 86790. DOI: 10.1128/MCB.21.6.1973-1985.2001. View

Boissinot S, Entezam A, Furano A . Selection against deleterious LINE-1-containing loci in the human lineage. Mol Biol Evol. 2001; 18(6):926-35. DOI: 10.1093/oxfordjournals.molbev.a003893. View

Boissinot S, Furano A . Adaptive evolution in LINE-1 retrotransposons. Mol Biol Evol. 2001; 18(12):2186-94. DOI: 10.1093/oxfordjournals.molbev.a003765. View

Ostertag E, Kazazian Jr H . Twin priming: a proposed mechanism for the creation of inversions in L1 retrotransposition. Genome Res. 2001; 11(12):2059-65. PMC: 311219. DOI: 10.1101/gr.205701. View

Nigumann P, Redik K, Matlik K, Speek M . Many human genes are transcribed from the antisense promoter of L1 retrotransposon. Genomics. 2002; 79(5):628-34. DOI: 10.1006/geno.2002.6758. View

10.

Gilbert N, Lutz-Prigge S, Moran J . Genomic deletions created upon LINE-1 retrotransposition. Cell. 2002; 110(3):315-25. DOI: 10.1016/s0092-8674(02)00828-0. View

11.

Pavlicek A, Paces J, Zika R, Hejnar J . Length distribution of long interspersed nucleotide elements (LINEs) and processed pseudogenes of human endogenous retroviruses: implications for retrotransposition and pseudogene detection. Gene. 2002; 300(1-2):189-94. DOI: 10.1016/s0378-1119(02)01047-8. View

12.

Nelson P, Carnegie P, Martin J, Ejtehadi H, Hooley P, Roden D . Demystified. Human endogenous retroviruses. Mol Pathol. 2003; 56(1):11-8. PMC: 1187282. DOI: 10.1136/mp.56.1.11. View

13.

Brouha B, Schustak J, Badge R, Lutz-Prigge S, Farley A, Moran J . Hot L1s account for the bulk of retrotransposition in the human population. Proc Natl Acad Sci U S A. 2003; 100(9):5280-5. PMC: 154336. DOI: 10.1073/pnas.0831042100. View

14.

Dewannieux M, Esnault C, Heidmann T . LINE-mediated retrotransposition of marked Alu sequences. Nat Genet. 2003; 35(1):41-8. DOI: 10.1038/ng1223. View

15.

McCLINTOCK B . Controlling elements and the gene. Cold Spring Harb Symp Quant Biol. 1956; 21:197-216. DOI: 10.1101/sqb.1956.021.01.017. View

16.

Pinol-Roma S, Dreyfuss G . Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. Nature. 1992; 355(6362):730-2. DOI: 10.1038/355730a0. View

17.

Lutz S, Vincent B, Kazazian Jr H, Batzer M, Moran J . Allelic heterogeneity in LINE-1 retrotransposition activity. Am J Hum Genet. 2003; 73(6):1431-7. PMC: 1180405. DOI: 10.1086/379744. View

18.

Perepelitsa-Belancio V, Deininger P . RNA truncation by premature polyadenylation attenuates human mobile element activity. Nat Genet. 2003; 35(4):363-6. DOI: 10.1038/ng1269. View

19.

Lavie L, Maldener E, Brouha B, Meese E, Mayer J . The human L1 promoter: variable transcription initiation sites and a major impact of upstream flanking sequence on promoter activity. Genome Res. 2004; 14(11):2253-60. PMC: 525683. DOI: 10.1101/gr.2745804. View

20.

Vargas D, Nascimbene C, Krishnan C, Zimmerman A, Pardo C . Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2004; 57(1):67-81. DOI: 10.1002/ana.20315. View