APOBEC3G Oligomerization Is Associated with the Inhibition of Both Alu and LINE-1 Retrotransposition.docVIP

APOBEC3G Oligomerization Is Associated with the Inhibition of Both Alu and LINE-1 Retrotransposition , Masaru Yokoyama , Hideaki Fujita , Hironori Takayoshi Koyama1?, Juan Fernando Arias1?, Yukie Iwabu1 2 3 Sato , Kenzo Tokunaga 2 1* 1 Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan, 2 Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan, 3 Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki, Japan Abstract Alu and LINE-1 (L1), which constitute ~11% and ~17% of the human genome, respectively, are transposable non- LTR retroelements. They transpose not only in germ cells but also in somatic cells, occasionally causing cancer. We have previously demonstrated that antiretroviral restriction factors, human APOBEC3 (hA3) proteins (A–H), differentially inhibit L1 retrotransposition. In this present study, we found that hA3 members also restrict Alu retrotransposition at differential levels that correlate with those observed previously for L1 inhibition. Through deletion analyses based on the best-characterized hA3 member human APOBEC3G (hA3G), its N-terminal 30 amino acids were required for its inhibitory activity against Alu retrotransposition. The inhibitory effect of hA3G on Alu retrotransposition was associated with its oligomerization that was affected by the deletion of its N-terminal 30 amino acids. Through structural modeling, the amino acids 24 to 28 of hA3G were predicted to be located at the interface of the dimer. The mutation of these residues resulted in abrogated hA3G oligomerization, and consistently abolished the inhibitory activity of hA3G against Alu retrotransposition. Importantly, the anti-L1 activity of hA3G was also associat