RT Journal Article
T1 Mobilization of LINE-1 retrotransposons is restricted by Tex19.1 in mouse embryonic stem cells
A1 MacLennan, Marie
A1 Garcia-Canadas, Marta
A1 Reichmann, Judith
A1 Khazina, Elena
A1 Wagner, Gabriele
A1 Playfoot, Christopher J.
A1 Salvador-Palomeque, Carmen
A1 Mann, Abigail R.
A1 Peressini, Paula
A1 Sanchez, Laura
A1 Dobie, Karen
A1 Read, David
A1 Hung, Chao-Chun
A1 Eskeland, Ragnhild
A1 Meehan, Richard R.
A1 Weichenrieder, Oliver
A1 Luis Garcia-Perez, Jose
A1 Adams, Ian R.
K1 High-frequency retrotransposition
K1 Human l1 retrotransposition
K1 Piwi-interacting rnas
K1 End rule pathway
K1 Ubiquitin ligase
K1 Dna methylation
K1 Orf1 protein
K1 Transposable elements
K1 Chaperone activity
K1 Binding protein
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-ORF1 p. 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.
PB Elife sciences publications ltd
SN 2050-084X
YR 2017
FD 2017-08-14
LK http://hdl.handle.net/10668/19396
UL http://hdl.handle.net/10668/19396
LA en
DS RISalud
RD Apr 12, 2025