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.
Highlights
The apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3) proteins are cytidine deaminases related to AID and APOBEC1
It is generally believed that A3G has weak or no activity against LINE-1 retrotransposition, and the effect of A3F on LINE-1 retrotransposition is controversial [6, 36,37,38,39]. We demonstrate that both human A3B and A3DE are potent inhibitors of LINE-1 retrotransposition but have different LINE-1 ribonucleoprotein particles (RNPs)-targeting activities
EGFP was expressed only after the LINE-1 transcript was spliced and reverse-transcribed, its cDNA was inserted into the host genome, and the EGFP reporter gene was transcribed under the control of its own CMV promoter (Fig 1B)
Summary
The apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3) proteins are cytidine deaminases related to AID (activation-induced cytidine deaminase) and APOBEC1 (apolipoprotein B mRNA editing enzyme, catalytic polypeptide). The APOBEC3 (A3) family consists of seven family members (APOBEC3A, -B, -C, -DE, -F, -G, and–H) with diverse activities against a variety of retroviruses and endogenous retroelements. Certain A3 family members can potently suppress retrovirus replication by editing the viral genome during reverse transcription via cytidine deamination as well as other mechanisms [1,2,3,4,5,6,7]. In order to successfully replicate, HIV-1 encodes Vif to inactivate some of these A3 molecules. PLOS ONE | DOI:10.1371/journal.pone.0157220 July 18, 2016
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