Retrotransposition in tumors and brains

John L Goodier

LINE-1s (L1s), the only currently active autonomous mobile DNA in humans, occupy at least 17% of human DNA. Throughout evolution, the L1 has also been responsible for genomic insertion of thousands of processed pseudogenes and over one million nonautonomous retrotransposons called SINEs (mainly Alus and SVAs). The 6-kb human L1 has a 5'- untranslated region (UTR) that functions as an internal promoter, two open reading frames-ORF1, which encodes an RNA-binding protein, and ORF2, which expresses endonuclease and reverse transcriptase activities-and a 3'-UTR which ends in a poly(A) signal and tail. Most L1s are molecular fossils: truncated, rearranged or mutated. However, 80 to 100 remain potentially active in any human individual, and to date 101 de novo disease-causing germline retrotransposon insertions have been characterized. It is now clear that significant levels of retrotransposition occur not only in the human germline but also in some somatic cell types. Recent publications and new investigations under way suggest that this may especially be the case for cancers and neuronal cells. This commentary offers a few points to consider to aid in avoiding misinterpretation of data as these studies move forward.