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 R Mann; Paula Peressini; Laura Sanchez; Karen 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 R Mann, Paula Peressini, Laura Sanchez, Karen 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

Access to Document

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

1 Finished

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

Ian Adams
- Ian.Adamsigmm.ed.acuk
- Deanery of Molecular, Genetic and Population Health Sciences - Personal Chair of Germline Biology
- MRC Human Genetics Unit
Person: Academic: Research Active
Jose Garcia-Perez
- MRC Human Genetics Unit
Person: Academic: Research Active

Cite this

Maclennan, M., Garcia-Cañadas, M., Reichmann, J., Khazina, E., Wagner, G., Playfoot, C. J., Salvador-Palomeque, C., Mann, A. R., Peressini, P., Sanchez, L., 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, [e26152]. https://doi.org/10.7554/eLife.26152

Maclennan, Marie ; Garcia-Cañadas, Marta ; Reichmann, Judith ; Khazina, Elena ; Wagner, Gabriele ; Playfoot, Christopher J ; Salvador-Palomeque, Carmen ; Mann, Abigail R ; Peressini, Paula ; Sanchez, Laura ; Dobie, Karen ; Read, David ; Hung, Chao-Chun ; Eskeland, Ragnhild ; Meehan, Richard R. ; Weichenrieder, Oliver ; García-Pérez, Jose Luis ; Adams, Ian R. / Mobilization of LINE-1 Retrotransposons is Restricted by Tex19.1 in Mouse Embryonic Stem Cells. In: eLIFE. 2017 ; Vol. 6.

@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 Mann, {Abigail R} and Paula Peressini and Laura Sanchez and Karen Dobie 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",

publisher = "ELIFE SCIENCES PUBLICATIONS LTD",

}

Maclennan, M, Garcia-Cañadas, M, Reichmann, J, Khazina, E, Wagner, G, Playfoot, CJ, Salvador-Palomeque, C, Mann, AR, Peressini, P, Sanchez, L, 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

Mobilization of LINE-1 Retrotransposons is Restricted by Tex19.1 in Mouse Embryonic Stem Cells. / Maclennan, Marie; Garcia-Cañadas, Marta; Reichmann, Judith; Khazina, Elena; Wagner, Gabriele; Playfoot, Christopher J; Salvador-Palomeque, Carmen; Mann, Abigail R; Peressini, Paula; Sanchez, Laura; Dobie, Karen; Read, David; Hung, Chao-Chun; Eskeland, Ragnhild; Meehan, Richard R.; Weichenrieder, Oliver; García-Pérez, Jose Luis ; Adams, Ian R.

In: eLIFE, Vol. 6, e26152, 14.08.2017.

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

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 R

AU - Peressini, Paula

AU - Sanchez, Laura

AU - 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

VL - 6

JO - eLIFE

JF - eLIFE

SN - 2050-084X

M1 - e26152

ER -

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

Abstract

Access to Document

Fingerprint

Projects

HGU Core Award Apr 12 - MAr 18

Profiles

Ian Adams

Jose Garcia-Perez

Cite this