title: APOBEC3DE Inhibits LINE-1 Retrotransposition by Interacting with ORF1p and Influencing LINE Reverse Transcriptase Activity.
abstract: 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.
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin, China.
authors.forename: Weizi
authors.initials: W
authors.lastname: Liang
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin, China.
authors.forename: Wensu
authors.initials: W
authors.lastname: Yuan
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Song
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province, China.|Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin, China.|Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, United States of America.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yu
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
mesh_terms: D003564:Cytidine Deaminase / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D016366:Open Reading Frames; D012313:RNA / Q000235:genetics / Q000378:metabolism; D048348:Reverse Transcription; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism
chemical_list: D012261:Ribonucleoproteins; D012313:RNA; C578087:APOBEC3D protein, human; D003564:Cytidine Deaminase