The 5′ truncation of retrotransposon L1: a process of genome integrity

Long interspersed element 1 (LINE1/L1) is a family of non-LTR retrotransposons that is active in mammals and has expanded dramatically to become 17% of the human genome. L1 activity in humans was first discovered as spontaneous insertions resulting in Mendelian disease. In subsequent years, much has been learned about the 2 L1 encoded proteins (ORF1 and ORF2) and host factors involved in transposition. Research describing many aspects of integration has been captured in important review papers. However, we know of no review dedicated to what is perhaps one of the most unusual features of L1, the 5' truncation that removes most of its sequence in 95% of insertions. Many consider this to be a form of host defense. By removing large portions of L1 during integration, 5' truncation has limited L1-mediated expansion of the genome by approximately 5 Gb. In this review, we discuss size distribution of 5' truncations and how this varies depending on the age and subfamily of the element. Of particular value is the recent telomere to telomere assembly of ultra-long sequence reads that document 1 million copies of L1. Studies of L1 integration show that 5' truncation occurs in germ cells, somatic tissues, and cancer cells. In addition, nonhuman primates, rodents, insects, and yeast contain L1 family elements that exhibit 5' truncation. Experiments have identified host factors that restrict transposition activity and have led to compelling proposals for how 5' truncation occurs. The proposed mechanisms and their implications are discussed.