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Human long interspersed elements 1 (LINE-1 or L1) is the only autonomous non-LTR retroelement in humans and has been associated with genome instability, inherited genetic diseases, and the development of cancer. Certain human APOBEC3 family proteins are known to have LINE-1 restriction activity. The mechanisms by which APOBEC3 affects LINE-1 retrotransposition are not all well characterized; here, we confirm that both A3B and A3DE have a strong ability to inhibit LINE-1 retrotransposition. A3DE interacts with LINE-1 ORF1p to target LINE-1 ribonucleoprotein particles in an RNA-dependent manner. Moreover, A3DE binds to LINE-1 RNA and ORF1 protein in cell culture system. Fluorescence microscopy demonstrated that A3DE co-localizes with ORF1p in cytoplasm. Furthermore, A3DE inhibits LINE-1 reverse transcriptase activity in LINE-1 ribonucleoprotein particles in a cytidine deaminase-independent manner. In contrast, A3B has less inhibitory effects on LINE-1 reverse transcriptase activity despite its strong inhibition of LINE-1 retrotransposition. This study demonstrates that different A3 proteins have been evolved to inhibit LINE-1 activity through distinct mechanisms.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948907 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157220 | PLOS |
Mol Oncol
September 2025
Department of Internal Medicine - Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Retroelements in the human genome are silenced via multiple mechanisms, including DNA methylation, to prevent their potential mutagenic effect. Retroelement activity, demonstrated by their expression and somatic retrotransposition events, was shown to be deregulated in multiple tumors but not yet in leukemia. We hypothesized that treatment with hypomethylating agents, commonly used in myelodysplastic syndromes and acute myeloid leukemia, could lead to increased retroelement activity and somatic retrotranspositions, thus contributing to disease progression.
View Article and Find Full Text PDFEMBO Rep
August 2025
Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
The cyclic dinucleotide sensor stimulator of interferon (IFN) genes (STING) is known for its critical role in interferon and inflammatory responses. In addition, STING also has functions independent of interferon induction. In this study, we report that STING restricts the mobilization of the cellular retrotransposon long interspersed nuclear element 1 (LINE-1) independent of cGAS and interferon induction.
View Article and Find Full Text PDFBiol Open
September 2025
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Reactivation of transposable elements (TEs) in somatic tissues, particularly of LINE-1, is associated with disease by causing gene mutations and DNA damage. Previous work has shown that the PIWI pathway is crucial for TE suppression in the germline. However, the status and function of this pathway is not well characterized in differentiated somatic cells and there is a lack of consensus on the role of the pathway in somatic tumorigenesis.
View Article and Find Full Text PDFNPJ Precis Oncol
July 2025
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA.
Although long interspersed element-1 (LINE-1) retrotransposons are poor prognostic indicators of non-small cell lung cancer, the genetic consequences of aberrant LINE-1 expression remain poorly understood. In this study, human bronchial epithelial cells were exposed chronically to 25 µM NiCl₂ to induce malignant transformation and compared to PBS-treated control cells or lung cancer cell lines. A 4 kb intronic LINE-1 insertion into the NACC2 (nucleus accumbens-associated protein 2) locus in nickel-transformed cells was associated with significant reductions in NACC2 mRNA and protein, along with constitutive increases in HDM2 and TP53α mRNAs, and aberrant expression of TP53β and TP53γ mRNAs.
View Article and Find Full Text PDFNature
August 2025
European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
Genomic structural variants (SVs) contribute substantially to genetic diversity and human diseases, yet remain under-characterized in population-scale cohorts. Here we conducted long-read sequencing in 1,019 humans to construct an intermediate-coverage resource covering 26 populations from the 1000 Genomes Project. Integrating linear and graph genome-based analyses, we uncover over 100,000 sequence-resolved biallelic SVs and we genotype 300,000 multiallelic variable number of tandem repeats, advancing SV characterization over short-read-based population-scale surveys.
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