New Insights into the Functional Role of Retrotransposon Dynamics in Mammalian Somatic Cells

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2021 May 15

PMID 33990851

Citations 6

Authors

Arianna Mangiavacchi

Peng Liu

Francesco Della Valle

Valerio Orlando

Affiliations

Soon will be listed here.

Abstract

Retrotransposons are genetic elements present across all eukaryotic genomes. While their role in evolution is considered as a potentially beneficial natural source of genetic variation, their activity is classically considered detrimental due to their potentially harmful effects on genome stability. However, studies are increasingly shedding light on the regulatory function and beneficial role of somatic retroelement reactivation in non-pathological contexts. Here, we review recent findings unveiling the regulatory potential of retrotransposons, including their role in noncoding RNA transcription, as modulators of mammalian transcriptional and epigenome landscapes. We also discuss technical challenges in deciphering the multifaceted activity of retrotransposable elements, highlighting an unforeseen central role of this neglected portion of the genome both in early development and in adult life.

Citing Articles

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References

Venter J, Adams M, Myers E, Li P, Mural R, Sutton G . The sequence of the human genome. Science. 2001; 291(5507):1304-51. DOI: 10.1126/science.1058040. View

Wicker T, Sabot F, Hua-Van A, Bennetzen J, Capy P, Chalhoub B . A unified classification system for eukaryotic transposable elements. Nat Rev Genet. 2007; 8(12):973-82. DOI: 10.1038/nrg2165. View

Cordaux R, Batzer M . The impact of retrotransposons on human genome evolution. Nat Rev Genet. 2009; 10(10):691-703. PMC: 2884099. DOI: 10.1038/nrg2640. View

Stocking C, Kozak C . Murine endogenous retroviruses. Cell Mol Life Sci. 2008; 65(21):3383-98. PMC: 4802364. DOI: 10.1007/s00018-008-8497-0. View

Gagnier L, Belancio V, Mager D . Mouse germ line mutations due to retrotransposon insertions. Mob DNA. 2019; 10:15. PMC: 6466679. DOI: 10.1186/s13100-019-0157-4. View

Dewannieux M, Harper F, Richaud A, Letzelter C, Ribet D, Pierron G . Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements. Genome Res. 2006; 16(12):1548-56. PMC: 1665638. DOI: 10.1101/gr.5565706. View

Friedli M, Trono D . The developmental control of transposable elements and the evolution of higher species. Annu Rev Cell Dev Biol. 2015; 31:429-51. DOI: 10.1146/annurev-cellbio-100814-125514. View

Feng Q, Moran J, Kazazian Jr H, Boeke J . Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition. Cell. 1996; 87(5):905-16. DOI: 10.1016/s0092-8674(00)81997-2. View

Mathias S, Scott A, Kazazian Jr H, Boeke J, Gabriel A . Reverse transcriptase encoded by a human transposable element. Science. 1991; 254(5039):1808-10. DOI: 10.1126/science.1722352. View

10.

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

11.

Richardson S, Morell S, Faulkner G . L1 retrotransposons and somatic mosaicism in the brain. Annu Rev Genet. 2014; 48:1-27. DOI: 10.1146/annurev-genet-120213-092412. View

12.

Denli A, Narvaiza I, Kerman B, Pena M, Benner C, Marchetto M . Primate-specific ORF0 contributes to retrotransposon-mediated diversity. Cell. 2015; 163(3):583-93. DOI: 10.1016/j.cell.2015.09.025. View

13.

Sookdeo A, Hepp C, McClure M, Boissinot S . Revisiting the evolution of mouse LINE-1 in the genomic era. Mob DNA. 2013; 4(1):3. PMC: 3600994. DOI: 10.1186/1759-8753-4-3. View

14.

Payer L, Burns K . Transposable elements in human genetic disease. Nat Rev Genet. 2019; 20(12):760-772. DOI: 10.1038/s41576-019-0165-8. View

15.

Mills R, Bennett E, Iskow R, Devine S . Which transposable elements are active in the human genome?. Trends Genet. 2007; 23(4):183-91. DOI: 10.1016/j.tig.2007.02.006. View

16.

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

17.

Raiz J, Damert A, Chira S, Held U, Klawitter S, Hamdorf M . The non-autonomous retrotransposon SVA is trans-mobilized by the human LINE-1 protein machinery. Nucleic Acids Res. 2011; 40(4):1666-83. PMC: 3287187. DOI: 10.1093/nar/gkr863. View

18.

Hancks D, Goodier J, Mandal P, Cheung L, Kazazian Jr H . Retrotransposition of marked SVA elements by human L1s in cultured cells. Hum Mol Genet. 2011; 20(17):3386-400. PMC: 3153304. DOI: 10.1093/hmg/ddr245. View

19.

Dewannieux M, Heidmann T . L1-mediated retrotransposition of murine B1 and B2 SINEs recapitulated in cultured cells. J Mol Biol. 2005; 349(2):241-7. DOI: 10.1016/j.jmb.2005.03.068. View

20.

Thompson P, Macfarlan T, Lorincz M . Long Terminal Repeats: From Parasitic Elements to Building Blocks of the Transcriptional Regulatory Repertoire. Mol Cell. 2016; 62(5):766-76. PMC: 4910160. DOI: 10.1016/j.molcel.2016.03.029. View