LINE-1 retrotransposable element ORF1 protein (L1ORF1p)

In humans, all new retrotransposition events are catalysed by LINE-1 (L1) elements. Active L1s encode two proteins strictly required for retrotransposition: ORF1p is an RNA binding protein with nucleic acid chaperone activity, and ORF2p is a multidomain protein with reverse transcriptase and endonuclease activities. Both these proteins interact directly or indirectly with various cellular factors and are incorporated into ribonucleoprotein particles (RNPs) along with the L1 RNA. L1 mobilization may be more prevalent in pluripotent cells in pre-implantation embryos rather than in lineage-restricted germ cells, and regulation of L1 activity in the pluripotent phase of the germline cycle is therefore likely to have a significant effect on trans-generational genome stability. DNA methylation in particular plays a key role in transcriptionally repressing L1 in the germline, and it is not clear how L1 activity is controlled in pluripotent cells and fetal germ cells while they are DNA hypomethylated.