Mobilization of LINE-1 Retrotransposons is Restricted by Tex19.1 in Mouse Embryonic Stem Cells

Marie Maclennan; Marta Garcia-Cañadas; Judith Reichmann; Elena Khazina; Gabriele Wagner; Christopher J Playfoot; Carmen Salvador-Palomeque; Abigail Mann; Paula Peressini; Laura Sanchez; Karen Thomas (nee Dobie); David Read; Chao-Chun Hung; Ragnhild Eskeland; Richard R. Meehan; Oliver Weichenrieder; Jose Luis García-Pérez; Ian R. Adams

doi:10.7554/eLife.26152

Mobilization of LINE-1 Retrotransposons is Restricted by Tex19.1 in Mouse Embryonic Stem Cells

Marie Maclennan, Marta Garcia-Cañadas, Judith Reichmann, Elena Khazina, Gabriele Wagner, Christopher J Playfoot, Carmen Salvador-Palomeque, Abigail Mann, Paula Peressini, Laura Sanchez, Karen Thomas (nee Dobie), David Read, Chao-Chun Hung, Ragnhild Eskeland, Richard R. Meehan, Oliver Weichenrieder, Jose Luis García-Pérez, Ian R. Adams

Research output: Contribution to journal › Article › peer-review

Abstract

Mobilization of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution, but these mutagenic events can also cause genetic disorders. In humans, retrotransposon mobilization is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early in development. Here we show that TEX19.1, which is induced by developmentally programmed DNA hypomethylation, can directly interact with the L1-encoded protein L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1 mobilization. We also show that TEX19.1 likely acts, at least in part, through promoting the activity of the E3 ubiquitin ligase UBR2 towards L1-ORF1p. Moreover, loss of Tex19.1 increases L1-ORF1p levels and L1 mobilization in pluripotent mouse embryonic stem cells, implying that Tex19.1 prevents de novo retrotransposition in the pluripotent phase of the germline cycle. These data show that post-translational regulation of L1 retrotransposons plays a key role in maintaining trans-generational genome stability in mammals.

Original language	English
Article number	e26152
Number of pages	32
Journal	eLIFE
Volume	6
DOIs	https://doi.org/10.7554/eLife.26152
Publication status	Published - 14 Aug 2017

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10.7554/eLife.26152Licence: Creative Commons: Attribution (CC-BY)

HGU Core Award Apr 12 - MAr 18
Hastie, N. (Principal Investigator), Adams, I. (Co-investigator), Baldock, R. (Co-investigator), Bickmore, W. (Co-investigator), Caceres, J. (Co-investigator), Dorin, J. (Co-investigator), FitzPatrick, D. (Co-investigator), Haley, C. (Co-investigator), Hill, B. (Co-investigator), Jackson, I. (Co-investigator), Jackson, A. (Co-investigator), Kudla, G. (Co-investigator), Meehan, R. (Co-investigator) & Patton, E. (Co-investigator)
MRC
1/04/12 → 31/03/18
Project: Research

Ian Adams
- MRC Human Genetics Unit
- Royal (Dick) School of Veterinary Studies - Chair position in Reproductive Biotechnologies
- Institute of Genetics and Cancer
Person: Academic: Research Active

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Maclennan, M., Garcia-Cañadas, M., Reichmann, J., Khazina, E., Wagner, G., Playfoot, C. J., Salvador-Palomeque, C., Mann, A., Peressini, P., Sanchez, L., Thomas (nee Dobie), K., Read, D., Hung, C.-C., Eskeland, R., Meehan, R. R., Weichenrieder, O., García-Pérez, J. L., & Adams, I. R. (2017). Mobilization of LINE-1 Retrotransposons is Restricted by Tex19.1 in Mouse Embryonic Stem Cells. eLIFE, 6, Article e26152. https://doi.org/10.7554/eLife.26152

@article{43df5feca2c9498d866977746fca7e66,

title = "Mobilization of LINE-1 Retrotransposons is Restricted by Tex19.1 in Mouse Embryonic Stem Cells",

abstract = "Mobilization of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution, but these mutagenic events can also cause genetic disorders. In humans, retrotransposon mobilization is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early in development. Here we show that TEX19.1, which is induced by developmentally programmed DNA hypomethylation, can directly interact with the L1-encoded protein L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1 mobilization. We also show that TEX19.1 likely acts, at least in part, through promoting the activity of the E3 ubiquitin ligase UBR2 towards L1-ORF1p. Moreover, loss of Tex19.1 increases L1-ORF1p levels and L1 mobilization in pluripotent mouse embryonic stem cells, implying that Tex19.1 prevents de novo retrotransposition in the pluripotent phase of the germline cycle. These data show that post-translational regulation of L1 retrotransposons plays a key role in maintaining trans-generational genome stability in mammals.",

author = "Marie Maclennan and Marta Garcia-Ca{\~n}adas and Judith Reichmann and Elena Khazina and Gabriele Wagner and Playfoot, {Christopher J} and Carmen Salvador-Palomeque and Abigail Mann and Paula Peressini and Laura Sanchez and {Thomas (nee Dobie)}, Karen and David Read and Chao-Chun Hung and Ragnhild Eskeland and Meehan, {Richard R.} and Oliver Weichenrieder and Garc{\'i}a-P{\'e}rez, {Jose Luis} and Adams, {Ian R.}",

year = "2017",

month = aug,

day = "14",

doi = "10.7554/eLife.26152",

language = "English",

volume = "6",

journal = "eLIFE",

issn = "2050-084X",

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Maclennan, M, Garcia-Cañadas, M, Reichmann, J, Khazina, E, Wagner, G, Playfoot, CJ, Salvador-Palomeque, C, Mann, A, Peressini, P, Sanchez, L, Thomas (nee Dobie), K, Read, D, Hung, C-C, Eskeland, R, Meehan, RR, Weichenrieder, O, García-Pérez, JL & Adams, IR 2017, 'Mobilization of LINE-1 Retrotransposons is Restricted by Tex19.1 in Mouse Embryonic Stem Cells', eLIFE, vol. 6, e26152. https://doi.org/10.7554/eLife.26152

TY - JOUR

T1 - Mobilization of LINE-1 Retrotransposons is Restricted by Tex19.1 in Mouse Embryonic Stem Cells

AU - Maclennan, Marie

AU - Garcia-Cañadas, Marta

AU - Reichmann, Judith

AU - Khazina, Elena

AU - Wagner, Gabriele

AU - Playfoot, Christopher J

AU - Salvador-Palomeque, Carmen

AU - Mann, Abigail

AU - Peressini, Paula

AU - Sanchez, Laura

AU - Thomas (nee Dobie), Karen

AU - Read, David

AU - Hung, Chao-Chun

AU - Eskeland, Ragnhild

AU - Meehan, Richard R.

AU - Weichenrieder, Oliver

AU - García-Pérez, Jose Luis

AU - Adams, Ian R.

PY - 2017/8/14

Y1 - 2017/8/14

N2 - Mobilization of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution, but these mutagenic events can also cause genetic disorders. In humans, retrotransposon mobilization is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early in development. Here we show that TEX19.1, which is induced by developmentally programmed DNA hypomethylation, can directly interact with the L1-encoded protein L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1 mobilization. We also show that TEX19.1 likely acts, at least in part, through promoting the activity of the E3 ubiquitin ligase UBR2 towards L1-ORF1p. Moreover, loss of Tex19.1 increases L1-ORF1p levels and L1 mobilization in pluripotent mouse embryonic stem cells, implying that Tex19.1 prevents de novo retrotransposition in the pluripotent phase of the germline cycle. These data show that post-translational regulation of L1 retrotransposons plays a key role in maintaining trans-generational genome stability in mammals.

AB - Mobilization of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution, but these mutagenic events can also cause genetic disorders. In humans, retrotransposon mobilization is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early in development. Here we show that TEX19.1, which is induced by developmentally programmed DNA hypomethylation, can directly interact with the L1-encoded protein L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1 mobilization. We also show that TEX19.1 likely acts, at least in part, through promoting the activity of the E3 ubiquitin ligase UBR2 towards L1-ORF1p. Moreover, loss of Tex19.1 increases L1-ORF1p levels and L1 mobilization in pluripotent mouse embryonic stem cells, implying that Tex19.1 prevents de novo retrotransposition in the pluripotent phase of the germline cycle. These data show that post-translational regulation of L1 retrotransposons plays a key role in maintaining trans-generational genome stability in mammals.

U2 - 10.7554/eLife.26152

DO - 10.7554/eLife.26152

M3 - Article

SN - 2050-084X

VL - 6

JO - eLIFE

JF - eLIFE

M1 - e26152

ER -

Mobilization of LINE-1 Retrotransposons is Restricted by Tex19.1 in Mouse Embryonic Stem Cells

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HGU Core Award Apr 12 - MAr 18

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Ian Adams

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