All APOBEC3 family proteins differentially inhibit LINE-1 retrotransposition.
Approximately 17% of the human genome is comprised of long interspersed nuclear element 1 (LINE-1, L1) non-LTR retrotransposons. L1 retrotransposition is known to be the cause of several genetic diseases, such as hemophilia A, Duchene muscular dystrophy, and so on. The L1 retroelements are also able to cause colon cancer, suggesting that L1 transposition could occur not only in germ cells, but also in somatic cells if innate immunity would not function appropriately. The mechanisms of L1 transposition restriction in the normal cells, however, are not fully defined. We here show that antiretroviral innate proteins, human APOBEC3 (hA3) family members, from hA3A to hA3H, differentially reduce the level of L1 retrotransposition that does not correlate either with antiviral activity against Vif-deficient HIV-1 and murine leukemia virus, or with patterns of subcellular localization. Importantly, hA3G protein inhibits L1 retrotransposition, in striking contrast to the recent reports. Inhibitory effect of hA3 family members on L1 transposition might not be due to deaminase activity, but due to novel mechanism(s). Thus, we conclude that all hA3 proteins act to differentially suppress uncontrolled transposition of L1 elements.
Kinomoto
Masanobu
M
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Kanno
Takayuki
T
Shimura
Mari
M
Ishizaka
Yukihito
Y
Kojima
Asato
A
Kurata
Takeshi
T
Sata
Tetsutaro
T
Tokunaga
Kenzo
K
D000071478:APOBEC Deaminases; D001483:Base Sequence; D002460:Cell Line; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000032:analysis / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D012190:Retroviridae / Q000502:physiology; D048348:Reverse Transcription; D017422:Sequence Analysis, DNA
D012333:RNA, Messenger; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase