Dataset Information

LINE-1 retrotransposition activity in human genomes.

ABSTRACT: Highly active (i.e., "hot") long interspersed element-1 (LINE-1 or L1) sequences comprise the bulk of retrotransposition activity in the human genome; however, the abundance of hot L1s in the human population remains largely unexplored. Here, we used a fosmid-based, paired-end DNA sequencing strategy to identify 68 full-length L1s that are differentially present among individuals but are absent from the human genome reference sequence. The majority of these L1s were highly active in a cultured cell retrotransposition assay. Genotyping 26 elements revealed that two L1s are only found in Africa and that two more are absent from the H952 subset of the Human Genome Diversity Panel. Therefore, these results suggest that hot L1s are more abundant in the human population than previously appreciated, and that ongoing L1 retrotransposition continues to be a major source of interindividual genetic variation.

SUBMITTER: Beck CR

PROVIDER: S-EPMC3013285 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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LINE-1 retrotransposition activity in human genomes.

Beck Christine R CR Collier Pamela P Macfarlane Catriona C Malig Maika M Kidd Jeffrey M JM Eichler Evan E EE Badge Richard M RM Moran John V JV

Cell 20100601 7

Highly active (i.e., "hot") long interspersed element-1 (LINE-1 or L1) sequences comprise the bulk of retrotransposition activity in the human genome; however, the abundance of hot L1s in the human population remains largely unexplored. Here, we used a fosmid-based, paired-end DNA sequencing strategy to identify 68 full-length L1s that are differentially present among individuals but are absent from the human genome reference sequence. The majority of these L1s were highly active in a cultured c ...[more]

PMID: 20602998

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Project description:Endogenous retrotransposons are considered the "molecular fossils" of ancient retroviral insertions. Several studies have indicated that host factors restrict both retroviruses and retrotransposons through different mechanisms. Type 1 long interspersed elements (LINE-1 or L1) are the only active retroelements that can replicate autonomously in the human genome. A recent study reported that LINE-1 retrotransposition is potently suppressed by BST2, a host restriction factor that prevents viral release mainly by physically tethering enveloped virions (such as HIV) to the surface of producer cells. However, no endoplasmic membrane structure has been associated with LINE-1 replication, suggesting that BST2 may utilize a distinct mechanism to suppress LINE-1. In this study, we showed that BST2 is a potent LINE-1 suppressor. Further investigations suggested that BST2 reduces the promoter activity of LINE-1 5' untranslated region (UTR) and lowers the levels of LINE-1 RNA, proteins, and events during LINE-1 retrotransposition. Surprisingly, although BST2 apparently uses different mechanisms against HIV and LINE-1, two membrane-associated domains that are essential for BST2-mediated HIV tethering also proved important for BST2-induced inhibition of LINE-1 5' UTR. Additionally, by suppressing LINE-1, BST2 prevented LINE-1-induced genomic DNA damage and innate immune activation. Taken together, our data uncovered the mechanism of BST2-mediated LINE-1 suppression and revealed new roles of BST2 as a promoter regulator, genome stabilizer, and innate immune suppressor. IMPORTANCE BST2 is a potent antiviral protein that suppresses the release of several enveloped viruses, mainly by tethering the envelope of newly synthesized virions and restraining them on the surface of producer cells. In mammalian cells, there are numerous DNA elements replicating through reverse transcription, among which LINE-1 is the only retroelement that can replicate autonomously. Although LINE-1 retrotransposition does not involve the participation of a membrane structure, BST2 has been reported as an efficient LINE-1 suppressor, suggesting a different mechanism for BST2-mediated LINE-1 inhibition and a new function for BST2 itself. We found that BST2 specifically represses the promoter activity of LINE-1 5' UTR, resulting in decreased levels of LINE-1 transcription, translation, and subsequent retrotransposition. Additionally, by suppressing LINE-1 activity, BST2 maintains genome stability and regulates innate immune activation. These findings expand our understanding of BST2 and its biological significance.

Dataset Information

LINE-1 retrotransposition activity in human genomes.

Publications

LINE-1 retrotransposition activity in human genomes.

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