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• W2082996197 endingPage "e1002842" @default.
• W2082996197 startingPage "e1002842" @default.
• W2082996197 abstract "Alu elements are trans-mobilized by the autonomous non-LTR retroelement, LINE-1 (L1). Alu-induced insertion mutagenesis contributes to about 0.1% human genetic disease and is responsible for the majority of the documented instances of human retroelement insertion-induced disease. Here we introduce a SINE recovery method that provides a complementary approach for comprehensive analysis of the impact and biological mechanisms of Alu retrotransposition. Using this approach, we recovered 226 de novo tagged Alu inserts in HeLa cells. Our analysis reveals that in human cells marked Alu inserts driven by either exogenously supplied full length L1 or ORF2 protein are indistinguishable. Four percent of de novo Alu inserts were associated with genomic deletions and rearrangements and lacked the hallmarks of retrotransposition. In contrast to L1 inserts, 5' truncations of Alu inserts are rare, as most of the recovered inserts (96.5%) are full length. De novo Alus show a random pattern of insertion across chromosomes, but further characterization revealed an Alu insertion bias exists favoring insertion near other SINEs, highly conserved elements, with almost 60% landing within genes. De novo Alu inserts show no evidence of RNA editing. Priming for reverse transcription rarely occurred within the first 20 bp (most 5') of the A-tail. The A-tails of recovered inserts show significant expansion, with many at least doubling in length. Sequence manipulation of the construct led to the demonstration that the A-tail expansion likely occurs during insertion due to slippage by the L1 ORF2 protein. We postulate that the A-tail expansion directly impacts Alu evolution by reintroducing new active source elements to counteract the natural loss of active Alus and minimizing Alu extinction." @default.
• W2082996197 created "2016-06-24" @default.
• W2082996197 creator A5015561999 @default.
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• W2082996197 creator A5055650523 @default.
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• W2082996197 date "2012-08-09" @default.
• W2082996197 modified "2023-09-27" @default.
• W2082996197 title "Rescuing Alu: Recovery of New Inserts Shows LINE-1 Preserves Alu Activity through A-Tail Expansion" @default.
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• W2082996197 doi "https://doi.org/10.1371/journal.pgen.1002842" @default.
• W2082996197 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3415434" @default.
• W2082996197 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22912586" @default.
• W2082996197 hasPublicationYear "2012" @default.
• W2082996197 type Work @default.

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