The challenge of ORF1p phosphorylation: Effects on L1 activity and its host.

L1 non-LTR retrotransposons are autonomously replicating genetic elements that profoundly affected their mammalian hosts having generated upwards of 40% or more of their genomes. Although deleterious, they remain active in most mammalian species, and thus the nature and consequences of the interaction between L1 and its host remain major issues for mammalian biology. We recently showed that L1 activity requires phosphorylation of one of its 2 encoded proteins, ORF1p, a nucleic acid chaperone and the major component of the L1RNP retrotransposition intermediate. Reversible protein phosphorylation, which is effected by interacting cascades of protein kinases, phosphatases, and ancillary proteins, is a mainstay in the regulation and coordination of many basic biological processes. Therefore, demonstrating phosphorylation-dependence of L1 activity substantially enlarged our knowledge of the scope of L1 / host interaction. However, developing a mechanistic understanding of what this means for L1 or its host is a formidable challenge, which we discuss here.