Human L1 retrotransposition: cis preference versus trans complementation

Long interspersed nuclear elements (LINEs or L1s) comprise approximately 17 % of human DNA; however, only about 60 of the similar to 400,000 L1s are mo bile, Using a retrotransposition assay in cultured human cells, we demonstr ate that. L1-encoded proteins predominantly mobilize the RNA that encodes t hem. At much lower levels, L1-encoded proteins can act in trails to promote retrotransposition of mutant L1s and other cellular mRNAs, creating proces sed pseudogenes. Mutant L1 RNAs are mobilized at 0.2 to 0.9% of the retrotr ansposition frequency of wild-type L1s, whereas cellular RNAs are mobilized at much lower frequencies (ca. 0.01 to 0.05% of wild-type levels). Thus, w e conclude that L1-encoded proteins demonstrate a profound cis preference f or their encoding RNA. This mechanism could enable L1 to remain retrotransp osition competent in the presence of the overwhelming number of nonfunction al L1s present in human DNA.