ArticleProceedings of the National Academy of Sciences of the United States of America2015
Phosphorylation of ORF1p is required for L1 retrotransposition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Ancient Persistence and Newfound Diversity of CR1-Group Retrotransposons Across Vertebrates.Genome biology and evolution · 2026Article
- Retrotransposon Protein L1 ORF1p Expression in Aging Central Nervous System.International journal of molecular sciences · 2025Article
- LINE-1 ribonucleoprotein condensates bind DNA to enable nuclear entry during mitosis.Science advances · 2025Article
- Diverse single-stranded nucleic acid binding proteins enable both stable protection and rapid exchange required for biological function.QRB discovery · 2025Article
- L1-ORF1p nucleoprotein can rapidly assume distinct conformations and simultaneously bind more than one nucleic acid.Nucleic acids research · 2024Article
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
- Downstream STING pathways IRF3 and NF-κB differentially regulate CCL22 in response to cytosolic dsDNA.Cancer gene therapy · 2024Article
- Nuclear cGAS restricts L1 retrotransposition by promoting TRIM41-mediated ORF2p ubiquitination and degradation.Nature communications · 2023Article
- Co-expression of distinct L1 retrotransposon coiled coils can lead to their entanglement.Mobile DNA · 2023Article
- Article
- Impact of retrotransposon protein L1 ORF1p expression on oncogenic pathways in hepatocellular carcinoma: the role of cytoplasmic PIN1 upregulation.British journal of cancer · 2023Article
- The L1-ORF1p coiled coil enables formation of a tightly compacted nucleic acid-bound complex that is associated with retrotransposition.Nucleic acids research · 2022Article
- Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19.International journal of molecular sciences · 2022Review
- Resveratrol blocks retrotransposition of LINE-1 through PPAR α and sirtuin-6.Scientific reports · 2022Article
- LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Role of long interspersed nuclear element-1 in the regulation of chromatin landscapes and genome dynamics.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Phase separation of the LINE-1 ORF1 protein is mediated by the N-terminus and coiled-coil domain.Biophysical journal · 2021Article
- Cryptic genetic variation enhances primate L1 retrotransposon survival by enlarging the functional coiled coil sequence space of ORF1p.PLoS genetics · 2020Article
- Human TRIM5α senses and restricts LINE-1 elements.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- LINE-1 ORF2p expression is nearly imperceptible in human cancers.Mobile DNA · 2020Article
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3 authors.
Funding
Abstract
Although members of the L1 (LINE-1) clade of non-LTR retrotransposons can be deleterious, the L1 clade has remained active in most mammals for ∼100 million years and generated almost 40% of the human genome. The details of L1-host interaction are largely unknown, however. Here we report that L1 activity requires phosphorylation of the protein encoded by the L1 ORF1 (ORF1p). Critical phospho-acceptor residues (two serines and two threonines) reside in four conserved proline-directed protein kinase (PDPK) target sites. The PDPK family includes mitogen-activated protein kinases and cyclin-dependent kinases. Mutation of any PDPK phospho-acceptor inhibits L1 retrotransposition. The phosphomimetic aspartic acid can restore activity at the two serine sites, but not at either threonine site, where it is strongly inhibitory. ORF1p also contains conserved PDPK docking sites, which promote specific interaction of PDPKs with their targets. As expected, mutations in these sites also inhibit L1 activity. PDPK mutations in ORF1p that inactivate L1 have no significant effect on the ability of ORF1p to anneal RNA in vitro, an important biochemical property of the protein. We show that phosphorylated PDPK sites in ORF1p are required for an interaction with the peptidyl prolyl isomerase 1 (Pin1), a critical component of PDPK-mediated regulation. Pin1 acts via isomerization of proline side chains at phosphorylated PDPK motifs, thereby affecting substrate conformation and activity. Our demonstration that L1 activity is dependent on and integrated with cellular phosphorylation regulatory cascades significantly increases our understanding of interactions between L1 and its host.
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