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Two additional potential retrotransposons isolated from a human L1 subfamily that contains an active retrotransposable element.

ABSTRACT: We have previously reported the isolation of a human retrotransposable L1 element. This element, allele L1.2B at the LRE-1 locus of chromosome 22, was shown by nucleotide sequence identity to be the direct precursor of a de novo retrotransposition event into the factor VIII gene on the X chromosome, resulting in hemophilia A in patient JH-27. We now report the isolation of the two remaining full-length members of the subfamily of L1 elements closely related to L1.2B present in the genome of the mother of JH-27. Since these elements, L1.3 and L1.4, are very similar in sequence to L1.2B and contain both open reading frames 1 and 2 intact, they are also likely to be active retrotransposable elements. This suggests that certain L1 subfamilies may contain multiple active elements.

SUBMITTER: Dombroski BA

PROVIDER: S-EPMC46962 | biostudies-other | 1993 Jul

REPOSITORIES: biostudies-other

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Two additional potential retrotransposons isolated from a human L1 subfamily that contains an active retrotransposable element.

Dombroski B A BA Scott A F AF Kazazian H H HH

Proceedings of the National Academy of Sciences of the United States of America 19930701 14

We have previously reported the isolation of a human retrotransposable L1 element. This element, allele L1.2B at the LRE-1 locus of chromosome 22, was shown by nucleotide sequence identity to be the direct precursor of a de novo retrotransposition event into the factor VIII gene on the X chromosome, resulting in hemophilia A in patient JH-27. We now report the isolation of the two remaining full-length members of the subfamily of L1 elements closely related to L1.2B present in the genome of the ...[more]

PMID: 8393568

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Project description:BackgroundPatients with systemic lupus erythematosus (SLE) have autoantibodies against the L1-encoded open-reading frame 1 protein (ORF1p). Here, we report (i) which immune cells ORF1p emanates from, (ii) which L1 loci are transcriptionally active, (iii) whether the cells express L1-dependent interferon and interferon-stimulated genes, and (iv) the effect of inhibition of L1 ORF2p by reverse transcriptase inhibitors.ResultsL1 ORF1p was detected by flow cytometry primarily in SLE CD66b+CD15+ regular and low-density granulocytes, but much less in other immune cell lineages. The amount of ORF1p was higher in neutrophils from patients with SLE disease activity index (SLEDAI) > 6 (p = 0.011) compared to patients with inactive disease, SLEDAI < 4. Patient neutrophils transcribed seven to twelve human-specific L1 loci (L1Hs), but only 3 that are full-length and with an intact ORF1. Besides serving as a source of detectable ORF1p, the most abundant transcript encoded a truncated ORF2p reverse transcriptase predicted to remain cytosolic, while the two other encoded an intact full-length ORF2p. A number of genes encoding proteins that influence L1 transcription positively or negatively were altered in patients, particularly those with active disease, compared to healthy controls. Components of nucleic acid sensing and interferon induction were also altered. SLE neutrophils also expressed type I interferon-inducible genes and interferon β, which were substantially reduced after treatment of the cells with drugs known to inhibit ORF2p reverse transcriptase activity.ConclusionsWe identified L1Hs loci that are transcriptionally active in SLE neutrophils, and a reduction in the epigenetic silencing mechanisms that normally counteract L1 transcription. SLE neutrophils contained L1-encoded ORF1p protein, as well as activation of the type I interferon system, which was inhibited by treatment with reverse transcriptase inhibitors. Our findings will enable a deeper analysis of L1 dysregulation and its potential role in SLE pathogenesis.

Dataset Information

Two additional potential retrotransposons isolated from a human L1 subfamily that contains an active retrotransposable element.

Publications

Two additional potential retrotransposons isolated from a human L1 subfamily that contains an active retrotransposable element.

Similar Datasets

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