Deamination-independent restriction of LINE-1 retrotransposition by APOBEC3H.

The APOBEC3 family of cytosine deaminase enzymes are able to restrict replication of retroelements， such as LINE-1. However， each of the seven APOBEC3 enzymes have been reported to act differentially to prevent LINE-1 retrotransposition and the mechanisms of APOBEC3-mediated LINE-1 inhibition has not been well understood. The prevailing view for many years was that APOBEC3-mediated LINE-1 inhibition was deamination-independent and relied on APOBEC3s blocking the LINE-1 reverse transcriptase DNA polymerization or transport of the LINE-1 RNA into the nucleus. However， recently it was shown that APOBEC3A can deaminate cytosine， to form uracil， on transiently exposed single-stranded LINE-1 cDNA and this leads to LINE-1 cDNA degradation. In this study， we confirmed that APOBEC3A is a potent deamination-dependent inhibitor of LINE-1 retrotransposition， but show that in contrast， A3H haplotype II and haplotype V restrict LINE-1 activity using a deamination-independent mechanism. Our study supports the model that different APOBEC3 proteins have evolved to inhibit LINE-1 retrotransposition through distinct mechanisms.