Structural mechanism of LINE-1 target-primed reverse transcription.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40048554.
- Also identified by DOI 10.1126/science.ads8412 and PMC identifier 7617806.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Long interspersed element-1 (LINE-1) retrotransposons are the only active autonomous transposable elements in humans. They propagate by reverse transcribing their messenger RNA into new genomic locations by a process called target-primed reverse transcription (TPRT). In this work, we present four cryo-electron microscopy structures of the human LINE-1 TPRT complex, revealing the conformational dynamics of open reading frame 2 protein (ORF2p) and its extensive remodeling of the target DNA for TPRT initiation. We observe nicking of the DNA second strand during reverse transcription of the first strand. Structure prediction identifies high-confidence binding sites for LINE-1-associated factors-namely proliferating cell nuclear antigen (PCNA) and cytoplasmic poly(A)-binding protein 1 (PABPC1)-on ORF2p. Together with our structural data, this suggests a mechanism by which these factors regulate retrotransposition and supports a model for TPRT that accounts for retrotransposition outcomes observed in cells.
Medical subject headings
- Long Interspersed Nucleotide Elements
- Reverse Transcription