Differential inhibition of long interspersed element 1 by APOBEC3 does not correlate with high-molecular-mass-complex formation or P-body association.
The human cytidine deaminase APOBEC3G (A3G) and other APOBEC3 proteins exhibit differential inhibitory activities against diverse endogenous retroelements and retroviruses, including Vif-deficient human immunodeficiency virus type 1. The potential inhibitory activity of human APOBEC proteins against long interspersed element 1 (LINE-1) has not been fully evaluated. Here, we demonstrate inhibition of LINE-1 by multiple human APOBEC3 cytidine deaminases, including previously unreported activity for A3DE and A3G. More ancient members of APOBEC, cytidine deaminases AID and APOBEC2, had no detectable activity against LINE-1. A3A, which did not form high-molecular-mass (HMM) complexes and interacted poorly with P bodies, was the most potent inhibitor of LINE-1. A3A specifically recognizes LINE-1 RNA but not the other cellular RNAs tested. However, in the presence of LINE-1, A3A became associated with HMM complexes containing LINE-1 RNA. The ability of A3A to recognize LINE-1 RNA required its catalytic domain and was important for its LINE-1 suppression. Although the mechanism of LINE-1 restriction did not seem to involve DNA editing, A3A inhibited the accumulation of nascent LINE-1 DNA, suggesting interference with LINE-1 reverse transcription and/or integration or intracellular movement of LINE-1 ribonucleoprotein. Thus, association with P bodies or cellular HMM complexes could not predict the potency of APOBEC3 anti-LINE-1 activities. The catalytic domain of APOBEC3 proteins may be important for proper folding and target factors such as RNA or protein interaction in addition to cytidine deamination.
Niewiadomska
Anna Maria
AM
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Tian
Chunjuan
C
Tan
Lindi
L
Wang
Tao
T
Sarkis
Phuong Thi Nguyen
PT
Yu
Xiao-Fang
XF
D000071478:APOBEC Deaminases; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism; D043525:Cytosine Deaminase / Q000378:metabolism*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D046911:Macromolecular Substances / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D046911:Macromolecular Substances; D009124:Muscle Proteins; D016601:RNA-Binding Proteins; D012313:RNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C120388:APOBEC2 protein, human; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase